Variant 9-22447072-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_022160.3(DMRTA1):c.7C>T(p.Arg3Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 1,608,318 control chromosomes in the GnomAD database, including 22 homozygotes. 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 0.0029 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0042 ( 19 hom. )

Consequence

DMRTA1
NM_022160.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.935

Variant links:

Genes affected

DMRTA1 (HGNC:13826): (DMRT like family A1) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in germ cell development; regulation of transcription by RNA polymerase II; and sex differentiation. Predicted to act upstream of or within male mating behavior and ovarian follicle development. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DMRTA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00441435).

BP6

Variant 9-22447072-C-T is Benign according to our data. Variant chr9-22447072-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 769751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMRTA1	NM_022160.3 linkuse as main transcript	c.7C>T	p.Arg3Trp	missense_variant	1/2	ENST00000325870.3	NP_071443.2	Q5VZB9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMRTA1	ENST00000325870.3 linkuse as main transcript	c.7C>T	p.Arg3Trp	missense_variant	1/2	1	NM_022160.3	ENSP00000319651.1		Q5VZB9

Frequencies

GnomAD3 genomes

AF:

0.00292

AC:

445

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00438

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00438

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00283

AC:

665

AN:

234798

Hom.:

AF XY:

0.00277

AC XY:

357

AN XY:

128908

show subpopulations

Gnomad AFR exome

AF:

0.000974

Gnomad AMR exome

AF:

0.00263

Gnomad ASJ exome

AF:

0.000311

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00356

Gnomad NFE exome

AF:

0.00446

Gnomad OTH exome

AF:

0.00328

GnomAD4 exome

AF:

0.00420

AC:

6110

AN:

1456000

Hom.:

Cov.:

AF XY:

0.00399

AC XY:

2889

AN XY:

724076

show subpopulations

Gnomad4 AFR exome

AF:

0.000698

Gnomad4 AMR exome

AF:

0.00288

Gnomad4 ASJ exome

AF:

0.000424

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00371

Gnomad4 NFE exome

AF:

0.00499

Gnomad4 OTH exome

AF:

0.00361

GnomAD4 genome

AF:

0.00292

AC:

445

AN:

152318

Hom.:

Cov.:

AF XY:

0.00286

AC XY:

213

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.00438

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00411

Hom.:

Bravo

AF:

0.00306

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000275

AC:

ESP6500EA

AF:

0.00362

AC:

ExAC

AF:

0.00241

AC:

284

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 01, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.050

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.67

M_CAP

Benign

0.034

MetaRNN

Benign

0.0044

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.90

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.64

REVEL

Benign

0.080

Sift

Uncertain

0.011

Sift4G

Uncertain

0.028

Polyphen

0.99

Vest4

0.27

MVP

0.66

MPC

0.30

ClinPred

0.033

GERP RS

3.2

Varity_R

0.089

gMVP

0.22

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