Variant 9-22447184-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_022160.3(DMRTA1):c.119G>C(p.Gly40Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,597,954 control chromosomes in the GnomAD database, including 22 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 (★★).

Frequency

Genomes: 𝑓 0.0070 ( 13 hom., cov: 33)

Exomes 𝑓: 0.00066 ( 9 hom. )

Consequence

DMRTA1
NM_022160.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.209

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027674437).

BP6

Variant 9-22447184-G-C is Benign according to our data. Variant chr9-22447184-G-C is described in ClinVar as [Benign]. Clinvar id is 785281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00701 (1068/152272) while in subpopulation AFR AF= 0.0233 (969/41576). AF 95% confidence interval is 0.0221. There are 13 homozygotes in gnomad4. There are 506 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMRTA1	NM_022160.3 linkuse as main transcript	c.119G>C	p.Gly40Ala	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.119G>C	p.Gly40Ala	missense_variant	1/2	1	NM_022160.3	ENSP00000319651.1		Q5VZB9

Frequencies

GnomAD3 genomes

AF:

0.00701

AC:

1067

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

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:

0.0000588

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00122

AC:

264

AN:

216308

Hom.:

AF XY:

0.000955

AC XY:

115

AN XY:

120412

show subpopulations

Gnomad AFR exome

AF:

0.0229

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000689

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000191

GnomAD4 exome

AF:

0.000663

AC:

959

AN:

1445682

Hom.:

Cov.:

AF XY:

0.000590

AC XY:

424

AN XY:

719014

show subpopulations

Gnomad4 AFR exome

AF:

0.0253

Gnomad4 AMR exome

AF:

0.00133

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000587

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000995

Gnomad4 OTH exome

AF:

0.00154

GnomAD4 genome

AF:

0.00701

AC:

1068

AN:

152272

Hom.:

Cov.:

AF XY:

0.00680

AC XY:

506

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0233

Gnomad4 AMR

AF:

0.00503

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.000673

Hom.:

Bravo

AF:

0.00842

ESP6500AA

AF:

0.0193

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00156

AC:

183

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 02, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.11

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.3

REVEL

Benign

0.011

Sift

Benign

0.063

Sift4G

Benign

0.35

Polyphen

0.0030

Vest4

0.11

MVP

0.20

MPC

0.17

ClinPred

0.0047

GERP RS

2.3

Varity_R

0.040

gMVP

0.37

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