Variant X-72872538-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_033053.3(DMRTC1):c.493C>T(p.Pro165Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000963 in 1,080,405 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00097 ( 0 hom., 0 hem., cov: 18)

Exomes 𝑓: 0.00096 ( 0 hom. 4 hem. )

Consequence

DMRTC1
NM_033053.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.282

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0057533383).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMRTC1	NM_033053.3 linkuse as main transcript	c.493C>T	p.Pro165Ser	missense_variant	7/7	ENST00000615063.2	NP_149042.2	Q5HYR2-1A0A024R4F7
DMRTC1	NM_001386923.1 linkuse as main transcript	c.412C>T	p.Pro138Ser	missense_variant	7/7		NP_001373852.1
DMRTC1	NM_001386924.1 linkuse as main transcript	c.412C>T	p.Pro138Ser	missense_variant	6/6		NP_001373853.1
DMRTC1	NR_170342.1 linkuse as main transcript	n.789C>T		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.493C>T	p.Pro165Ser	missense_variant	7/7	3	NM_033053.3	ENSP00000484718.2		Q5HYR2-1A0A087X258

Frequencies

GnomAD3 genomes

AF:

0.000974

AC:

104

AN:

106809

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

30875

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000298

Gnomad ASJ

AF:

0.000764

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00167

Gnomad OTH

AF:

0.000683

GnomAD3 exomes

AF:

0.000899

AC:

AN:

74558

Hom.:

AF XY:

0.00

AC XY:

AN XY:

19176

show subpopulations

Gnomad AFR exome

AF:

0.000301

Gnomad AMR exome

AF:

0.0000889

Gnomad ASJ exome

AF:

0.000437

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000844

Gnomad NFE exome

AF:

0.00167

Gnomad OTH exome

AF:

0.00188

GnomAD4 exome

AF:

0.000961

AC:

936

AN:

973558

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

284854

show subpopulations

Gnomad4 AFR exome

AF:

0.000197

Gnomad4 AMR exome

AF:

0.000243

Gnomad4 ASJ exome

AF:

0.000132

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000874

Gnomad4 NFE exome

AF:

0.00110

Gnomad4 OTH exome

AF:

0.00105

GnomAD4 genome

AF:

0.000973

AC:

104

AN:

106847

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

30929

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.000298

Gnomad4 ASJ

AF:

0.000764

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00167

Gnomad4 OTH

AF:

0.000675

Alfa

AF:

0.00108

Hom.:

ESP6500AA

AF:

0.000845

AC:

ESP6500EA

AF:

0.000774

AC:

ExAC

AF:

0.000221

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

Jun 17, 2024

The c.493C>T (p.P165S) alteration is located in exon 6 (coding exon 6) of the DMRTC1 gene. This alteration results from a C to T substitution at nucleotide position 493, causing the proline (P) at amino acid position 165 to be replaced by a serine (S). 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

0.12

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.070

.;T

FATHMM_MKL

Benign

0.015

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

.;L

PrimateAI

Uncertain

0.55

Sift4G

Uncertain

0.053

T;T

Vest4

0.15

MVP

0.030

ClinPred

0.013

GERP RS

1.1

Varity_R

0.14

gMVP

0.051

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

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