Variant chrX-72872519-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_033053.3(DMRTC1):c.512G>A(p.Arg171His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000068 ( 0 hom., 0 hem., cov: 18)

Exomes 𝑓: 0.000062 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

DMRTC1
NM_033053.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.519

Variant links:

Genes affected

DMRTC1 (HGNC:13910): (DMRT like family C1) Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DMRTC1 links:

DMRTC1 (HGNC:):

DMRTC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.034468174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMRTC1	NM_033053.3 linkuse as main transcript	c.512G>A	p.Arg171His	missense_variant	7/7	ENST00000615063.2	NP_149042.2	Q5HYR2-1A0A024R4F7
DMRTC1	NM_001386923.1 linkuse as main transcript	c.431G>A	p.Arg144His	missense_variant	7/7		NP_001373852.1
DMRTC1	NM_001386924.1 linkuse as main transcript	c.431G>A	p.Arg144His	missense_variant	6/6		NP_001373853.1
DMRTC1	NR_170342.1 linkuse as main transcript	n.808G>A		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMRTC1	ENST00000615063.2 linkuse as main transcript	c.512G>A	p.Arg171His	missense_variant	7/7	3	NM_033053.3	ENSP00000484718.2		Q5HYR2-1A0A087X258

Frequencies

GnomAD3 genomes

AF:

0.0000685

AC:

AN:

102200

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

27726

show subpopulations

Gnomad AFR

AF:

0.0000384

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000970

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

98384

Hom.:

AF XY:

0.00

AC XY:

AN XY:

21878

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000128

Gnomad ASJ exome

AF:

0.000267

Gnomad EAS exome

AF:

0.000146

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000942

Gnomad OTH exome

AF:

0.000367

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000620

AC:

AN:

1032214

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

319474

show subpopulations

Gnomad4 AFR exome

AF:

0.0000449

Gnomad4 AMR exome

AF:

0.0000769

Gnomad4 ASJ exome

AF:

0.0000587

Gnomad4 EAS exome

AF:

0.000118

Gnomad4 SAS exome

AF:

0.0000434

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000654

Gnomad4 OTH exome

AF:

0.0000463

GnomAD4 genome

AF:

0.0000685

AC:

AN:

102200

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

27726

show subpopulations

Gnomad4 AFR

AF:

0.0000384

Gnomad4 AMR

AF:

0.000105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000970

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000978

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2024

The c.512G>A (p.R171H) alteration is located in exon 6 (coding exon 6) of the DMRTC1 gene. This alteration results from a G to A substitution at nucleotide position 512, causing the arginine (R) at amino acid position 171 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.89

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

.;T

FATHMM_MKL

Benign

0.0036

M_CAP

Benign

0.022

MetaRNN

Benign

0.034

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;L

PrimateAI

Uncertain

0.51

Sift4G

Benign

0.088

T;T

Vest4

0.12

MVP

0.061

ClinPred

0.094

GERP RS

1.1

Varity_R

0.049

gMVP

0.029

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over