9-842568-C-G

Position:

• chr9-842568-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_021951.3(DMRT1):​c.354+376C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00513 in 220,096 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0062 (3 hom.)
• Consequence: DMRT1 NM_021951.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0930

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-842568-C-G is Benign according to our data. Variant chr9-842568-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2659025.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 706 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMRT1	NM_021951.3	c.354+376C>G		intron_variant		ENST00000382276.8	NP_068770.2
DMRT1	XM_006716732.2	c.354+376C>G		intron_variant			XP_006716795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMRT1	ENST00000382276.8	c.354+376C>G		intron_variant		1	NM_021951.3	ENSP00000371711.3
DMRT1	ENST00000564322.1	n.503+376C>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00464 AC: 707 AN: 152220 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00785

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.00367

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00645

Gnomad OTH AF: 0.0143

GnomAD4 exome AF: 0.00624 AC: 423 AN: 67762 Hom.: 3 AF XY: 0.00590 AC XY: 211 AN XY: 35756

Gnomad4 AFR exome AF: 0.00266

Gnomad4 AMR exome AF: 0.00669

Gnomad4 ASJ exome AF: 0.000573

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00467

Gnomad4 FIN exome AF: 0.00743

Gnomad4 NFE exome AF: 0.00715

Gnomad4 OTH exome AF: 0.00530

GnomAD4 genome AF: 0.00463 AC: 706 AN: 152334 Hom.: 2 Cov.: 33 AF XY: 0.00432 AC XY: 322 AN XY: 74484

Gnomad4 AFR AF: 0.00113

Gnomad4 AMR AF: 0.00784

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.00367

Gnomad4 NFE AF: 0.00645

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00513 Hom.: 1

Bravo AF: 0.00493

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

DMRT1: BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.2
DANN	Benign	0.73

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: rs189459273; hg19: chr9-842568;