9-841825-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021951.3(DMRT1):c.-14C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,603,638 control chromosomes in the GnomAD database, including 22,782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2085 hom., cov: 32)
  • Exomes 𝑓: 0.15 (20697 hom.)
• Consequence: DMRT1 NM_021951.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.418

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 9-841825-C-T is Benign according to our data. Variant chr9-841825-C-T is described in ClinVar as [Benign]. Clinvar id is 1280767.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMRT1	NM_021951.3	c.-14C>T		5_prime_UTR_variant	1/5	ENST00000382276.8
DMRT1	XM_006716732.2	c.-14C>T		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMRT1	ENST00000382276.8	c.-14C>T		5_prime_UTR_variant	1/5	1	NM_021951.3	P1
DMRT1	ENST00000564322.1	n.136C>T		non_coding_transcript_exon_variant	1/3	1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22433 AN: 152120 Hom.: 2076 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.165

GnomAD3 exomes AF: 0.182 AC: 41872 AN: 229898 Hom.: 4815 AF XY: 0.182 AC XY: 22795 AN XY: 124946

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.193

Gnomad ASJ exome AF: 0.207

Gnomad EAS exome AF: 0.471

Gnomad SAS exome AF: 0.251

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.155 AC: 224827 AN: 1451400 Hom.: 20697 Cov.: 35 AF XY: 0.157 AC XY: 113496 AN XY: 720990

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.194

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.475

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.148 AC: 22457 AN: 152238 Hom.: 2085 Cov.: 32 AF XY: 0.150 AC XY: 11169 AN XY: 74428

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.172

Alfa AF: 0.146 Hom.: 394

Bravo AF: 0.150

Asia WGS AF: 0.367 AC: 1277 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	12
Dann	Benign	0.80

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: rs3739584; hg19: chr9-841825; COSMIC: COSV66520800; COSMIC: COSV66520800;