Variant chr9-846952-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_021951.3(DMRT1):c.355-8G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,614,048 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 45 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 34 hom. )

Consequence

DMRT1
NM_021951.3 splice_region, intron

Scores

Splicing: ADA: 0.00001418

Clinical Significance

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

Conservation

PhyloP100: 2.13

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 9-846952-G-C is Benign according to our data. Variant chr9-846952-G-C is described in ClinVar as [Benign]. Clinvar id is 768275.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 = 0.013 (1977/152314) while in subpopulation AFR AF= 0.0428 (1779/41562). AF 95% confidence interval is 0.0411. There are 45 homozygotes in gnomad4. There are 916 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1977 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMRT1	NM_021951.3 link	c.355-8G>C		splice_region_variant, intron_variant		ENST00000382276.8	NP_068770.2	Q9Y5R6-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
DMRT1	ENST00000382276.8 link	c.355-8G>C	splice_region_variant, intron_variant	1	NM_021951.3	ENSP00000371711.3	Q9Y5R6-1
DMRT1	ENST00000569227.1 link	c.-120-8G>C	splice_region_variant, intron_variant	1		ENSP00000454701.1	H3BN61
DMRT1	ENST00000564322.1 link	n.504-8G>C	splice_region_variant, intron_variant	1

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1960

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0425

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00792

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00399

AC:

997

AN:

249900

Hom.:

AF XY:

0.00320

AC XY:

432

AN XY:

135182

show subpopulations

Gnomad AFR exome

AF:

0.0432

Gnomad AMR exome

AF:

0.00442

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.000712

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00176

AC:

2571

AN:

1461734

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

1162

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.0392

Gnomad4 AMR exome

AF:

0.00474

Gnomad4 ASJ exome

AF:

0.00295

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000564

Gnomad4 OTH exome

AF:

0.00431

GnomAD4 genome

AF:

0.0130

AC:

1977

AN:

152314

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

916

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0428

Gnomad4 AMR

AF:

0.00791

Gnomad4 ASJ

AF:

0.00289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000617

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.00438

Hom.:

Bravo

AF:

0.0146

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.00107

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 12, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0020

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