chrX-72875278-C-T

Position:

• chrX-72875278-C-T

Variant summary

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

The NM_033053.3(DMRTC1):​c.118G>A​(p.Glu40Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: DMRTC1 NM_033053.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.36

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.038101733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMRTC1	NM_033053.3	c.118G>A	p.Glu40Lys	missense_variant	3/7	ENST00000615063.2	NP_149042.2
DMRTC1	NM_001386923.1	c.37G>A	p.Glu13Lys	missense_variant	3/7		NP_001373852.1
DMRTC1	NM_001386924.1	c.37G>A	p.Glu13Lys	missense_variant	2/6		NP_001373853.1
DMRTC1	NR_170342.1	n.475G>A		non_coding_transcript_exon_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMRTC1	ENST00000615063.2	c.118G>A	p.Glu40Lys	missense_variant	3/7	3	NM_033053.3	ENSP00000484718.2
DMRTC1	ENST00000595412.5	c.118G>A	p.Glu40Lys	missense_variant	2/6	1		ENSP00000471224.1
DMRTC1	ENST00000596389.5	c.118G>A	p.Glu40Lys	missense_variant	3/5	1		ENSP00000469615.1
DMRTC1	ENST00000622727.4	n.118G>A		non_coding_transcript_exon_variant	3/6	1		ENSP00000482641.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 2824 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 484

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ExAC AF: 0.0000168 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 30, 2023

The c.118G>A (p.E40K) alteration is located in exon 2 (coding exon 2) of the DMRTC1 gene. This alteration results from a G to A substitution at nucleotide position 118, causing the glutamic acid (E) at amino acid position 40 to be replaced by a lysine (K). 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	0.069
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.2
DANN	Benign	0.47
DEOGEN2	Benign	0.0087	.;T;.
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.46	.;.;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.038	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.14	N;N;.
PrimateAI	Benign	0.32	T
Sift4G	Benign	0.12	T;T;.
Vest4		0.056
MVP		0.014
ClinPred		0.025	T
GERP RS		-0.75
Varity_R		0.043
gMVP		0.037

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: rs782746813; hg19: chrX-72095112;