11-60415512-T-A

Position:

• chr11-60415512-T-A

Variant summary

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

The NM_032597.5(MS4A14):​c.544T>A​(p.Phe182Ile) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MS4A14 NM_032597.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.910

Genes affected

MS4A14 (HGNC:30706): (membrane spanning 4-domains A14) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.28685027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MS4A14	NM_032597.5	c.544T>A	p.Phe182Ile	missense_variant	5/5	ENST00000300187.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MS4A14	ENST00000300187.11	c.544T>A	p.Phe182Ile	missense_variant	5/5	1	NM_032597.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 32

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 18, 2022

The c.544T>A (p.F182I) alteration is located in exon 5 (coding exon 5) of the MS4A14 gene. This alteration results from a T to A substitution at nucleotide position 544, causing the phenylalanine (F) at amino acid position 182 to be replaced by an isoleucine (I). 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	Uncertain	0.34
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	.;.;T;.;.
Eigen	Benign	0.049
Eigen_PC	Benign	-0.083
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.52	T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.29	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	.;.;M;.;.
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.4	D;.;D;D;D
REVEL	Benign	0.090
Sift	Pathogenic	0.0	D;.;D;D;D
Sift4G	Uncertain	0.027	D;D;D;D;D
Polyphen		1.0	.;.;D;D;.
Vest4		0.43
MutPred		0.44		.;.;Loss of catalytic residue at F182 (P = 0.1556);.;.;
MVP		0.12
MPC		0.31
ClinPred		0.95	D
GERP RS		2.6
Varity_R		0.15

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: chr11-60182985;