11-60501133-T-A

Position:

• chr11-60501133-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017716.3(MS4A12):​c.365T>A​(p.Phe122Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MS4A12 NM_017716.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.437

Genes affected

MS4A12 (HGNC:13370): (membrane spanning 4-domains A12) The protein encoded by this gene is a cell surface protein found primarily in the apical membrane of colonocytes. Silencing of this gene in colon cancer cells inhibits the proliferation, cell motility, and chemotactic invasion of cells. This gene is part of a cluster of similar genes found on chromosome 11. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39946696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MS4A12	NM_017716.3	c.365T>A	p.Phe122Tyr	missense_variant	3/7	ENST00000016913.8	NP_060186.2
MS4A12	XM_011545117.3	c.365T>A	p.Phe122Tyr	missense_variant	4/8		XP_011543419.1
MS4A12	NM_001164470.2	c.277-850T>A		intron_variant			NP_001157942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MS4A12	ENST00000016913.8	c.365T>A	p.Phe122Tyr	missense_variant	3/7	1	NM_017716.3	ENSP00000016913	P1
MS4A12	ENST00000526784.5	c.277-850T>A		intron_variant		3		ENSP00000431959
MS4A12	ENST00000537076.5	c.277-850T>A		intron_variant		5		ENSP00000440424
MS4A12	ENST00000530007.1			downstream_gene_variant		3		ENSP00000434783

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Dec 20, 2023

The c.365T>A (p.F122Y) alteration is located in exon 3 (coding exon 2) of the MS4A12 gene. This alteration results from a T to A substitution at nucleotide position 365, causing the phenylalanine (F) at amino acid position 122 to be replaced by a tyrosine (Y). 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	0.25
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.53
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.57	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.17
Sift	Benign	0.69	T
Sift4G	Benign	0.57	T
Polyphen		0.56	P
Vest4		0.24
MutPred		0.86		Gain of sheet (P = 0.0477);
MVP		0.040
MPC		0.22
ClinPred		0.14	T
GERP RS		1.7
Varity_R		0.078

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: chr11-60268606;