Genetic Variant DMRT1:c.354+125delC (chr9-842315-AC-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_021951.3(DMRT1):c.354+125delC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 11873 hom., cov: 0)

Exomes 𝑓: 0.45 ( 114541 hom. )

Consequence

DMRT1
NM_021951.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0990

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 -10 ACMG points.

BP6

Variant 9-842315-AC-A is Benign according to our data. Variant chr9-842315-AC-A is described in ClinVar as [Benign]. Clinvar id is 1253599.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMRT1	NM_021951.3 link	c.354+125delC		intron_variant	Intron 1 of 4	ENST00000382276.8	NP_068770.2	Q9Y5R6-1
DMRT1	XM_006716732.2 link	c.354+125delC		intron_variant	Intron 1 of 4		XP_006716795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMRT1	ENST00000382276.8 link	c.354+124delC		intron_variant	Intron 1 of 4	1	NM_021951.3	ENSP00000371711.3		Q9Y5R6-1
DMRT1	ENST00000564322.1 link	n.503+124delC		intron_variant	Intron 1 of 2	1

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

56890

AN:

148108

Hom.:

11876

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.520

Gnomad AMR

AF:

0.362

Gnomad ASJ

AF:

0.468

Gnomad EAS

AF:

0.213

Gnomad SAS

AF:

0.373

Gnomad FIN

AF:

0.456

Gnomad MID

AF:

0.401

Gnomad NFE

AF:

0.481

Gnomad OTH

AF:

0.409

GnomAD3 exomes

AF:

0.390

AC:

32032

AN:

82146

Hom.:

6807

AF XY:

0.399

AC XY:

17769

AN XY:

44588

show subpopulations

Gnomad AFR exome

AF:

0.205

Gnomad AMR exome

AF:

0.332

Gnomad ASJ exome

AF:

0.497

Gnomad EAS exome

AF:

0.200

Gnomad SAS exome

AF:

0.380

Gnomad FIN exome

AF:

0.442

Gnomad NFE exome

AF:

0.475

Gnomad OTH exome

AF:

0.414

GnomAD4 exome

AF:

0.447

AC:

494058

AN:

1104166

Hom.:

114541

Cov.:

AF XY:

0.447

AC XY:

246629

AN XY:

551732

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.324

Gnomad4 ASJ exome

AF:

0.487

Gnomad4 EAS exome

AF:

0.235

Gnomad4 SAS exome

AF:

0.382

Gnomad4 FIN exome

AF:

0.467

Gnomad4 NFE exome

AF:

0.471

Gnomad4 OTH exome

AF:

0.425

GnomAD4 genome

AF:

0.384

AC:

56891

AN:

148192

Hom.:

11873

Cov.:

AF XY:

0.382

AC XY:

27569

AN XY:

72132

show subpopulations

Gnomad4 AFR

AF:

0.221

Gnomad4 AMR

AF:

0.362

Gnomad4 ASJ

AF:

0.468

Gnomad4 EAS

AF:

0.212

Gnomad4 SAS

AF:

0.374

Gnomad4 FIN

AF:

0.456

Gnomad4 NFE

AF:

0.481

Gnomad4 OTH

AF:

0.403

Alfa

AF:

0.412

Hom.:

1390

Asia WGS

AF:

0.254

AC:

881

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 21, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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