9-955794-C-T

Variant names:

• chr9-955794-C-T
• rs364477
• NM_021951.3:c.968-12191C>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.968-12191C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,140 control chromosomes in the GnomAD database, including 46,312 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 0.78 (46312 hom., cov: 33)
• Consequence: DMRT1 NM_021951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661
• Publications: 13 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMRT1	NM_021951.3	c.968-12191C>T		intron_variant	Intron 4 of 4	ENST00000382276.8	NP_068770.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMRT1	ENST00000382276.8	c.968-12191C>T		intron_variant	Intron 4 of 4	1	NM_021951.3	ENSP00000371711.3
DMRT1	ENST00000569227.1	c.494-12191C>T		intron_variant	Intron 4 of 4	1		ENSP00000454701.1

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118298 AN: 152022 Hom.: 46297 Cov.: 33

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.798

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

GnomAD4 genome AF: 0.778 AC: 118365 AN: 152140 Hom.: 46312 Cov.: 33 AF XY: 0.781 AC XY: 58066 AN XY: 74380

African (AFR) AF: 0.699 AC: 29004 AN: 41492

American (AMR) AF: 0.713 AC: 10897 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2931 AN: 3472

East Asian (EAS) AF: 0.806 AC: 4164 AN: 5166

South Asian (SAS) AF: 0.929 AC: 4477 AN: 4820

European-Finnish (FIN) AF: 0.849 AC: 8987 AN: 10588

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.812 AC: 55208 AN: 68006

Other (OTH) AF: 0.800 AC: 1686 AN: 2108

Alfa AF: 0.797 Hom.: 147467

Bravo AF: 0.761

Asia WGS AF: 0.856 AC: 2976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.89
PhyloP100		-0.66
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: rs364477; hg19: chr9-955794;