chrX-72874949-G-T

Position:

• chrX-72874949-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_033053.3(DMRTC1):​c.133C>A​(p.Gln45Lys) 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: 2)
• Consequence: DMRTC1 NM_033053.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.318

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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07568592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMRTC1	NM_033053.3	c.133C>A	p.Gln45Lys	missense_variant	4/7	ENST00000615063.2	NP_149042.2
DMRTC1	NM_001386923.1	c.52C>A	p.Gln18Lys	missense_variant	4/7		NP_001373852.1
DMRTC1	NM_001386924.1	c.52C>A	p.Gln18Lys	missense_variant	3/6		NP_001373853.1
DMRTC1	NR_170342.1	n.490C>A		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMRTC1	ENST00000615063.2	c.133C>A	p.Gln45Lys	missense_variant	4/7	3	NM_033053.3	ENSP00000484718.2
DMRTC1	ENST00000595412.5	c.133C>A	p.Gln45Lys	missense_variant	3/6	1		ENSP00000471224.1
DMRTC1	ENST00000596389.5	c.123+324C>A		intron_variant		1		ENSP00000469615.1
DMRTC1	ENST00000622727.4	n.133C>A		non_coding_transcript_exon_variant	4/6	1		ENSP00000482641.1

Frequencies

GnomAD3 genomes Cov.: 2

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 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

Nov 10, 2022

The c.133C>A (p.Q45K) alteration is located in exon 3 (coding exon 3) of the DMRTC1 gene. This alteration results from a C to A substitution at nucleotide position 133, causing the glutamine (Q) at amino acid position 45 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	0.086
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	14
DANN	Benign	0.90
DEOGEN2	Benign	0.027	T;.
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.36	.;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.076	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Benign	0.40	T
Sift4G	Benign	0.26	T;.
Vest4		0.21
MVP		0.040
ClinPred		0.065	T
GERP RS		0.45
Varity_R		0.32
gMVP		0.040

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-72094783;