NM_021951.3:c.538+16492C>T

Variant names:

• chr9-863635-C-T
• rs755383
• NM_021951.3:c.538+16492C>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.538+16492C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,934 control chromosomes in the GnomAD database, including 23,664 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 0.55 (23664 hom., cov: 32)
• Consequence: DMRT1 NM_021951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 42 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 (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021951.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMRT1	NM_021951.3	MANE Select	c.538+16492C>T		intron	N/A	NP_068770.2
	DMRT1	NM_001363767.1		c.64+16492C>T		intron	N/A	NP_001350696.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMRT1	ENST00000382276.8	TSL:1 MANE Select	c.538+16492C>T		intron	N/A	ENSP00000371711.3
	DMRT1	ENST00000569227.1	TSL:1	c.64+16492C>T		intron	N/A	ENSP00000454701.1
	DMRT1	ENST00000564322.1	TSL:1	n.687+16492C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83174 AN: 151816 Hom.: 23652 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.548 AC: 83217 AN: 151934 Hom.: 23664 Cov.: 32 AF XY: 0.545 AC XY: 40467 AN XY: 74260

African (AFR) AF: 0.385 AC: 15949 AN: 41418

American (AMR) AF: 0.566 AC: 8649 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2396 AN: 3470

East Asian (EAS) AF: 0.640 AC: 3301 AN: 5156

South Asian (SAS) AF: 0.601 AC: 2890 AN: 4808

European-Finnish (FIN) AF: 0.531 AC: 5594 AN: 10544

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42423 AN: 67954

Other (OTH) AF: 0.593 AC: 1249 AN: 2106

Alfa AF: 0.603 Hom.: 121576

Bravo AF: 0.543

Asia WGS AF: 0.609 AC: 2118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.3
DANN	Benign	0.51
PhyloP100		0.055
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: rs755383; hg19: chr9-863635;