rs6477419

Positions:

• chr9-989943-T-C
• chr9-989943-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000190165.3(DMRT3):​c.455-98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,480,712 control chromosomes in the GnomAD database, including 47,780 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 0.25 (5050 hom., cov: 32)
  • Exomes 𝑓: 0.25 (42730 hom.)
• Consequence: DMRT3 ENST00000190165.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250

Genes affected

DMRT3 (HGNC:13909): (doublesex and mab-3 related transcription factor 3) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in male sex differentiation and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including adult walking behavior; transmission of nerve impulse; and ventral spinal cord interneuron specification. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMRT3	NM_021240.4	c.455-98T>C		intron_variant		ENST00000190165.3	NP_067063.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMRT3	ENST00000190165.3	c.455-98T>C		intron_variant		1	NM_021240.4	ENSP00000190165	P1
DMRT3	ENST00000417254.1	c.-55T>C		5_prime_UTR_variant	1/1			ENSP00000387472

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37715 AN: 152004 Hom.: 5041 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.249 AC: 331217 AN: 1328592 Hom.: 42730 Cov.: 22 AF XY: 0.248 AC XY: 162279 AN XY: 654590

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.199

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.289

Gnomad4 SAS exome AF: 0.220

Gnomad4 FIN exome AF: 0.385

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.231

GnomAD4 genome AF: 0.248 AC: 37749 AN: 152120 Hom.: 5050 Cov.: 32 AF XY: 0.255 AC XY: 18995 AN XY: 74362

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.188

Alfa AF: 0.243 Hom.: 1007

Bravo AF: 0.232

Asia WGS AF: 0.247 AC: 861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.62

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: rs6477419; hg19: chr9-989943; COSMIC: COSV51903258;