rs11790408

Variant names:

• chr9-876418-G-T
• rs11790408
• NM_021951.3:c.539-17494G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• 46,XY disorder of sex development

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• 46,XX disorder of sex development

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DMRT1	NM_021951.3	c.539-17494G>T		intron_variant	Intron 2 of 4	ENST00000382276.8	NP_068770.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMRT1	ENST00000382276.8	c.539-17494G>T		intron_variant	Intron 2 of 4	1	NM_021951.3	ENSP00000371711.3
DMRT1	ENST00000569227.1	c.65-17494G>T		intron_variant	Intron 2 of 4	1		ENSP00000454701.1
DMRT1	ENST00000564322.1	n.688-17494G>T		intron_variant	Intron 2 of 2	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

African (AFR) AF: 0.114 AC: 4721 AN: 41492

American (AMR) AF: 0.332 AC: 5066 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1334 AN: 3468

East Asian (EAS) AF: 0.275 AC: 1417 AN: 5148

South Asian (SAS) AF: 0.299 AC: 1438 AN: 4808

European-Finnish (FIN) AF: 0.371 AC: 3900 AN: 10502

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27192 AN: 67936

Other (OTH) AF: 0.334 AC: 705 AN: 2108

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
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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