9-842315-AC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_021951.3(DMRT1):c.354+125del 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0990

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]

ACMG classification

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/exons	MANE	UniProt
DMRT1	NM_021951.3	c.354+125del		intron_variant		ENST00000382276.8
DMRT1	XM_006716732.2	c.354+125del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMRT1	ENST00000382276.8	c.354+125del		intron_variant		1	NM_021951.3	P1
DMRT1	ENST00000564322.1	n.503+125del		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 56890 AN: 148108 Hom.: 11876 Cov.: 0

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

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.: 0 AF XY: 0.447 AC XY: 246629 AN XY: 551732

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.: 0 AF XY: 0.382 AC XY: 27569 AN XY: 72132

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs56130013; hg19: chr9-842315;