chr9-846742-G-C

Position:

• chr9-846742-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021951.3(DMRT1):​c.355-218G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0561 in 152,230 control chromosomes in the GnomAD database, including 275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.056 (275 hom., cov: 32)
• Consequence: DMRT1 NM_021951.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.457

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 9-846742-G-C is Benign according to our data. Variant chr9-846742-G-C is described in ClinVar as [Benign]. Clinvar id is 1261311.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMRT1	NM_021951.3	c.355-218G>C		intron_variant		ENST00000382276.8	NP_068770.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMRT1	ENST00000382276.8	c.355-218G>C		intron_variant		1	NM_021951.3	ENSP00000371711.3
DMRT1	ENST00000569227.1	c.-120-218G>C		intron_variant		1		ENSP00000454701.1
DMRT1	ENST00000564322.1	n.504-218G>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0561 AC: 8531 AN: 152112 Hom.: 274 Cov.: 32

Gnomad AFR AF: 0.0622

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.0251

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.0515

Gnomad FIN AF: 0.0946

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0603

Gnomad OTH AF: 0.0401

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

GnomAD4 genome AF: 0.0561 AC: 8544 AN: 152230 Hom.: 275 Cov.: 32 AF XY: 0.0566 AC XY: 4216 AN XY: 74422

Gnomad4 AFR AF: 0.0624

Gnomad4 AMR AF: 0.0250

Gnomad4 ASJ AF: 0.0210

Gnomad4 EAS AF: 0.00598

Gnomad4 SAS AF: 0.0509

Gnomad4 FIN AF: 0.0946

Gnomad4 NFE AF: 0.0604

Gnomad4 OTH AF: 0.0397

Alfa AF: 0.0304 Hom.: 23

Bravo AF: 0.0510

Asia WGS AF: 0.0380 AC: 131 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12115433; hg19: chr9-846742;