9-842395-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.354+203C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00683 in 663,398 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (114 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (38 hom.)
• Consequence: DMRT1 NM_021951.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.162

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=-0.87).
• BP6: Variant 9-842395-C-T is Benign according to our data. Variant chr9-842395-C-T is described in ClinVar as [Benign]. Clinvar id is 1289213.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMRT1	NM_021951.3	c.354+203C>T		intron_variant		ENST00000382276.8
DMRT1	XM_006716732.2	c.354+203C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMRT1	ENST00000382276.8	c.354+203C>T		intron_variant		1	NM_021951.3	P1
DMRT1	ENST00000564322.1	n.503+203C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0213 AC: 3232 AN: 151978 Hom.: 111 Cov.: 32

Gnomad AFR AF: 0.0738

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00872

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0149

GnomAD3 exomes AF: 0.00740 AC: 367 AN: 49566 Hom.: 15 AF XY: 0.00630 AC XY: 159 AN XY: 25258

Gnomad AFR exome AF: 0.0760

Gnomad AMR exome AF: 0.00424

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000164

Gnomad OTH exome AF: 0.00282

GnomAD4 exome AF: 0.00249 AC: 1271 AN: 511304 Hom.: 38 Cov.: 6 AF XY: 0.00220 AC XY: 589 AN XY: 267826

Gnomad4 AFR exome AF: 0.0738

Gnomad4 AMR exome AF: 0.00494

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000199

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000184

Gnomad4 OTH exome AF: 0.00664

GnomAD4 genome AF: 0.0214 AC: 3262 AN: 152094 Hom.: 114 Cov.: 32 AF XY: 0.0213 AC XY: 1585 AN XY: 74370

Gnomad4 AFR AF: 0.0744

Gnomad4 AMR AF: 0.00870

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00287 Hom.: 0

Bravo AF: 0.0241

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

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.4
Dann	Benign	0.83

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: rs148624819; hg19: chr9-842395;