Variant 9-977054-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_021240.4(DMRT3):c.53C>A(p.Pro18Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,571,990 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0070 ( 19 hom., cov: 33)

Exomes 𝑓: 0.00070 ( 15 hom. )

Consequence

DMRT3
NM_021240.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.185

Variant links:

Genes affected

DMRT3 (HGNC:13909): (doublesex and mab-3 related transcription factor 3) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in male sex differentiation and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including adult walking behavior; transmission of nerve impulse; and ventral spinal cord interneuron specification. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DMRT3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046800375).

BP6

Variant 9-977054-C-A is Benign according to our data. Variant chr9-977054-C-A is described in ClinVar as [Benign]. Clinvar id is 720431.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00698 (1063/152228) while in subpopulation AFR AF= 0.0243 (1010/41570). AF 95% confidence interval is 0.0231. There are 19 homozygotes in gnomad4. There are 493 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMRT3	NM_021240.4 linkuse as main transcript	c.53C>A	p.Pro18Gln	missense_variant	1/2	ENST00000190165.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMRT3	ENST00000190165.3 linkuse as main transcript	c.53C>A	p.Pro18Gln	missense_variant	1/2	1	NM_021240.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00699

AC:

1064

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00146

AC:

260

AN:

178220

Hom.:

AF XY:

0.00104

AC XY:

103

AN XY:

98732

show subpopulations

Gnomad AFR exome

AF:

0.0263

Gnomad AMR exome

AF:

0.000907

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000136

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000703

AC:

998

AN:

1419762

Hom.:

Cov.:

AF XY:

0.000603

AC XY:

424

AN XY:

703558

show subpopulations

Gnomad4 AFR exome

AF:

0.0275

Gnomad4 AMR exome

AF:

0.00113

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000549

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.00698

AC:

1063

AN:

152228

Hom.:

Cov.:

AF XY:

0.00662

AC XY:

493

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0243

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00153

Hom.:

Bravo

AF:

0.00827

ESP6500AA

AF:

0.0192

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00168

AC:

194

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.66

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0047

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.5

REVEL

Benign

0.077

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.045

Polyphen

1.0

Vest4

0.28

MVP

0.68

MPC

0.36

ClinPred

0.036

GERP RS

3.8

Varity_R

0.10

gMVP

0.49

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