rs7040024

chr9-845516-A-Cchr9-845516-A-Gchr9-845516-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_021951.3(DMRT1):c.355-1444A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 151,914 control chromosomes in the GnomAD database, including 4,733 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (4733 hom., cov: 32)
• Consequence: DMRT1 NM_021951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMRT1	NM_021951.3	c.355-1444A>C		intron_variant		ENST00000382276.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMRT1	ENST00000382276.8	c.355-1444A>C		intron_variant		1	NM_021951.3	P1
DMRT1	ENST00000569227.1	c.-120-1444A>C		intron_variant		1
DMRT1	ENST00000564322.1	n.504-1444A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37627 AN: 151796 Hom.: 4723 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.243

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.248 AC: 37676 AN: 151914 Hom.: 4733 Cov.: 32 AF XY: 0.249 AC XY: 18513 AN XY: 74262

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.240

Alfa AF: 0.242 Hom.: 7615

Bravo AF: 0.247

Asia WGS AF: 0.202 AC: 701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	5.1
Dann	Benign	0.86

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: rs7040024; hg19: chr9-845516; COSMIC: COSV66523967;