Variant 9-842146-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021951.3(DMRT1):c.308A>G(p.Lys103Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,547,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

DMRT1
NM_021951.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.14

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.064017415).

BP6

Variant 9-842146-A-G is Benign according to our data. Variant chr9-842146-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2198711.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMRT1	NM_021951.3 link	c.308A>G	p.Lys103Arg	missense_variant	1/5	ENST00000382276.8	NP_068770.2	Q9Y5R6-1
DMRT1	XM_006716732.2 link	c.308A>G	p.Lys103Arg	missense_variant	1/5		XP_006716795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMRT1	ENST00000382276.8 link	c.308A>G	p.Lys103Arg	missense_variant	1/5	1	NM_021951.3	ENSP00000371711.3		Q9Y5R6-1
DMRT1	ENST00000564322.1 link	n.457A>G		non_coding_transcript_exon_variant	1/3	1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000228

AC:

AN:

149228

Hom.:

AF XY:

0.000294

AC XY:

AN XY:

81620

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000944

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000135

Gnomad OTH exome

AF:

0.000677

GnomAD4 exome

AF:

0.000127

AC:

177

AN:

1395424

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

106

AN XY:

689840

show subpopulations

Gnomad4 AFR exome

AF:

0.0000627

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000750

Gnomad4 FIN exome

AF:

0.0000264

Gnomad4 NFE exome

AF:

0.0000702

Gnomad4 OTH exome

AF:

0.000361

GnomAD4 genome

AF:

0.000112

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000624

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.000105

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 22, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

0.095

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.84

M_CAP

Benign

0.0060

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.95

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.4

REVEL

Benign

0.015

Sift

Benign

0.22

Sift4G

Benign

0.32

Polyphen

0.90

Vest4

0.28

MVP

0.27

MPC

0.41

ClinPred

0.062

GERP RS

4.2

Varity_R

0.34

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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