9-894044-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_021951.3(DMRT1):c.671A>G(p.Asn224Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00175 in 1,614,232 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 24 hom. )

Consequence

DMRT1
NM_021951.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: 6.66

Publications

8 publications found

Variant links:

Genes affected

DMRT1 (HGNC:2934): (doublesex and mab-3 related transcription factor 1) This gene is found in a cluster with two other members of the gene family, having in common a zinc finger-like DNA-binding motif (DM domain). The DM domain is an ancient, conserved component of the vertebrate sex-determining pathway that is also a key regulator of male development in flies and nematodes. This gene exhibits a gonad-specific and sexually dimorphic expression pattern. Defective testicular development and XY feminization occur when this gene is hemizygous. [provided by RefSeq, Jul 2008]

DMRT1 Gene-Disease associations (from GenCC):

46,XY disorder of sex development
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
46,XX disorder of sex development
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

DMRT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01156497).

BP6

Variant 9-894044-A-G is Benign according to our data. Variant chr9-894044-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 243009.

BS2

High AC in GnomAd4 at 224 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMRT1	NM_021951.3 link	c.671A>G	p.Asn224Ser	missense_variant	Exon 3 of 5	ENST00000382276.8	NP_068770.2	Q9Y5R6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DMRT1	ENST00000382276.8 link	c.671A>G	p.Asn224Ser	missense_variant	Exon 3 of 5	1	NM_021951.3	ENSP00000371711.3	Q9Y5R6-1
DMRT1	ENST00000569227.1 link	c.197A>G	p.Asn66Ser	missense_variant	Exon 3 of 5	1		ENSP00000454701.1	H3BN61
DMRT1	ENST00000564322.1 link	n.820A>G		non_coding_transcript_exon_variant	Exon 3 of 3	1

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

224

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00272

AC:

684

AN:

251454

AF XY:

0.00349

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.00466

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00137

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00178

AC:

2596

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

1598

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33480

American (AMR)

AF:

0.00125

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00474

AC:

124

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0124

AC:

1073

AN:

86258

European-Finnish (FIN)

AF:

0.00163

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00607

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000967

AC:

1075

AN:

1112010

Other (OTH)

AF:

0.00230

AC:

139

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

187

375

562

750

937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00147

AC:

224

AN:

152340

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

124

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41580

American (AMR)

AF:

0.00189

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00749

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.0122

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00141

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00106

AC:

AN:

68038

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00148

Hom.:

Bravo

AF:

0.000963

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00255

AC:

310

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00174

EpiControl

AF:

0.00273

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Sep 06, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 01, 2018

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 11, 2018

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Non-obstructive azoospermia

Uncertain:1

Jun 07, 2020

Institute of Reproductive Genetics, University of Münster

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.61

D;T

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;D

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.76

MutationAssessor

Pathogenic

3.1

M;.

PhyloP100

6.7

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.8

D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.022

D;D

Polyphen

0.98

D;.

Vest4

0.74

MVP

0.59

MPC

0.64

ClinPred

0.046

GERP RS

4.8

Varity_R

0.53

gMVP

0.34

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over