9-842032-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_021951.3(DMRT1):c.194C>T(p.Ala65Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000355 in 1,547,530 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A65G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 1 hom. )

Consequence

DMRT1
NM_021951.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.952

Publications

0 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:

ENSG00000294371 (HGNC:):

ENSG00000294371 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.070456624).

BS2

High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021951.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMRT1	NM_021951.3	MANE Select	c.194C>T	p.Ala65Val	missense	Exon 1 of 5	NP_068770.2	Q9Y5R6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DMRT1	ENST00000382276.8	TSL:1 MANE Select	c.194C>T	p.Ala65Val	missense	Exon 1 of 5	ENSP00000371711.3	Q9Y5R6-1
DMRT1	ENST00000564322.1	TSL:1	n.343C>T		non_coding_transcript_exon	Exon 1 of 3
ENSG00000294371	ENST00000723200.1		n.401+4823G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000352

AC:

AN:

142198

AF XY:

0.0000257

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000935

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000358

AC:

AN:

1395276

Hom.:

Cov.:

AF XY:

0.0000421

AC XY:

AN XY:

689032

show subpopulations

African (AFR)

AF:

0.000629

AC:

AN:

31816

American (AMR)

AF:

0.0000277

AC:

AN:

36108

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25184

East Asian (EAS)

AF:

0.00

AC:

AN:

36124

South Asian (SAS)

AF:

0.00

AC:

AN:

79850

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42152

Middle Eastern (MID)

AF:

0.000818

AC:

AN:

4890

European-Non Finnish (NFE)

AF:

0.0000185

AC:

AN:

1081168

Other (OTH)

AF:

0.0000862

AC:

AN:

57984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41558

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000944

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000282

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.060

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.42

M_CAP

Benign

0.0069

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

0.95

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.53

REVEL

Benign

0.049

Sift

Benign

0.26

Sift4G

Benign

0.14

Polyphen

0.14

Vest4

0.029

MutPred

0.13

Loss of relative solvent accessibility (P = 0.0404)

MVP

0.36

MPC

0.19

ClinPred

0.11

GERP RS

4.0

PromoterAI

0.0048

Neutral

(source)

Varity_R

0.095

gMVP

0.35

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over