9-876418-G-T

Position:

• chr9-876418-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021951.3(DMRT1):​c.539-17494G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,936 control chromosomes in the GnomAD database, including 8,235 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 0.30 (8235 hom., cov: 31)
• Consequence: DMRT1 NM_021951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.534

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMRT1	NM_021951.3	c.539-17494G>T		intron_variant		ENST00000382276.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMRT1	ENST00000382276.8	c.539-17494G>T		intron_variant		1	NM_021951.3	P1
DMRT1	ENST00000569227.1	c.65-17494G>T		intron_variant		1
DMRT1	ENST00000564322.1	n.688-17494G>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46185 AN: 151816 Hom.: 8233 Cov.: 31

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.304 AC: 46197 AN: 151936 Hom.: 8235 Cov.: 31 AF XY: 0.301 AC XY: 22383 AN XY: 74248

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.334

Alfa AF: 0.311 Hom.: 1570

Bravo AF: 0.295

Asia WGS AF: 0.257 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.67

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: rs11790408; hg19: chr9-876418; COSMIC: COSV66519908;