9-841971-T-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021951.3(DMRT1):c.133T>A(p.Ser45Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,583,340 control chromosomes in the GnomAD database, including 22,373 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.15 ( 2066 hom., cov: 32)

Exomes 𝑓: 0.15 ( 20307 hom. )

Consequence

DMRT1
NM_021951.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.90

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3878942E-4).

BP6

Variant 9-841971-T-A is Benign according to our data. Variant chr9-841971-T-A is described in ClinVar as [Benign]. Clinvar id is 1280947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMRT1	NM_021951.3 link	c.133T>A	p.Ser45Thr	missense_variant	Exon 1 of 5	ENST00000382276.8	NP_068770.2	Q9Y5R6-1
DMRT1	XM_006716732.2 link	c.133T>A	p.Ser45Thr	missense_variant	Exon 1 of 5		XP_006716795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMRT1	ENST00000382276.8 link	c.133T>A	p.Ser45Thr	missense_variant	Exon 1 of 5	1	NM_021951.3	ENSP00000371711.3		Q9Y5R6-1
DMRT1	ENST00000564322.1 link	n.282T>A		non_coding_transcript_exon_variant	Exon 1 of 3	1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22338

AN:

152036

Hom.:

2057

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.100

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.164

GnomAD3 exomes

AF:

0.191

AC:

36172

AN:

189484

Hom.:

4260

AF XY:

0.191

AC XY:

19970

AN XY:

104430

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.195

Gnomad ASJ exome

AF:

0.207

Gnomad EAS exome

AF:

0.480

Gnomad SAS exome

AF:

0.254

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.168

GnomAD4 exome

AF:

0.154

AC:

220532

AN:

1431186

Hom.:

20307

Cov.:

AF XY:

0.157

AC XY:

111160

AN XY:

709092

show subpopulations

Gnomad4 AFR exome

AF:

0.108

Gnomad4 AMR exome

AF:

0.194

Gnomad4 ASJ exome

AF:

0.205

Gnomad4 EAS exome

AF:

0.477

Gnomad4 SAS exome

AF:

0.251

Gnomad4 FIN exome

AF:

0.103

Gnomad4 NFE exome

AF:

0.135

Gnomad4 OTH exome

AF:

0.171

GnomAD4 genome

AF:

0.147

AC:

22362

AN:

152154

Hom.:

2066

Cov.:

AF XY:

0.150

AC XY:

11124

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.174

Gnomad4 ASJ

AF:

0.213

Gnomad4 EAS

AF:

0.471

Gnomad4 SAS

AF:

0.272

Gnomad4 FIN

AF:

0.100

Gnomad4 NFE

AF:

0.136

Gnomad4 OTH

AF:

0.172

Alfa

AF:

0.143

Hom.:

544

Bravo

AF:

0.150

TwinsUK

AF:

0.137

AC:

508

ALSPAC

AF:

0.135

AC:

519

ESP6500AA

AF:

0.0987

AC:

381

ESP6500EA

AF:

0.123

AC:

945

ExAC

AF:

0.163

AC:

18462

Asia WGS

AF:

0.367

AC:

1276

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.3

DANN

Benign

0.79

DEOGEN2

Benign

0.035

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.31

MetaRNN

Benign

0.00014

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.8

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.18

REVEL

Benign

0.013

Sift

Benign

0.47

Sift4G

Benign

0.49

Polyphen

0.016

Vest4

0.028

MPC

0.18

ClinPred

0.0027

GERP RS

-1.9

Varity_R

0.045

gMVP

0.35

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over