X-139596651-G-T

Position:

• chrX-139596651-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001171876.2(MCF2):​c.2403C>A​(p.His801Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: MCF2 NM_001171876.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.694

Genes affected

MCF2 (HGNC:6940): (MCF.2 cell line derived transforming sequence) The oncogenic protein encoded by this gene is a guanine nucleotide exchange factor (GEF) that exerts control over some members of the Rho family of small GTPases. Several transcript variants encoding different isoforms have been found for this gene. These isoforms exhibit different expression patterns and varying levels of GEF activity.[provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCF2	NM_001171876.2	c.2403C>A	p.His801Gln	missense_variant	23/29	ENST00000519895.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCF2	ENST00000519895.6	c.2403C>A	p.His801Gln	missense_variant	23/29	2	NM_001171876.2	P4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

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

Apr 22, 2024

The c.2403C>A (p.H801Q) alteration is located in exon 23 (coding exon 22) of the MCF2 gene. This alteration results from a C to A substitution at nucleotide position 2403, causing the histidine (H) at amino acid position 801 to be replaced by a glutamine (Q). 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	Pathogenic	0.63
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Uncertain	0.55	.;D;.;.;T;.;.;.
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.51	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.2	.;M;.;.;.;.;M;.
MutationTaster	Benign	0.92	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-7.6	.;D;D;D;D;D;D;D
REVEL	Benign	0.29
Sift	Benign	0.19	.;T;T;T;D;T;T;T
Sift4G	Uncertain	0.0020	.;D;D;D;D;D;D;D
Polyphen		0.99, 0.99, 1.0	.;D;.;.;.;.;D;D
Vest4		0.59, 0.62, 0.55, 0.59, 0.56, 0.58
MVP		0.59
MPC		0.64
ClinPred		0.99	D
GERP RS		-1.8
Varity_R		0.61
gMVP		0.97

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-138678810;