chr11-60178272-T-G

Position:

• chr11-60178272-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022349.4(MS4A6A):​c.327A>C​(p.Leu109Phe) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MS4A6A NM_022349.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549

Genes affected

MS4A6A (HGNC:13375): (membrane spanning 4-domains A6A) This gene encodes a member of the membrane-spanning 4A gene family. Members of this nascent protein family are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns among hematopoietic cells and nonlymphoid tissues. The gene encoding this protein is localized to 11q12.1, among a cluster of family members. Alternative splicing of this gene results in several transcript variants that encode different protein isoforms. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14492175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MS4A6A	NM_022349.4	c.327A>C	p.Leu109Phe	missense_variant	4/6	ENST00000528851.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MS4A6A	ENST00000528851.6	c.327A>C	p.Leu109Phe	missense_variant	4/6	1	NM_022349.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	6.8
DANN	Benign	0.26
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.56	T;T;T;T;.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.14	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.85	L;L;L;.;.;.
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.63	N;N;N;N;N;D
REVEL	Benign	0.037
Sift	Benign	0.11	T;T;T;D;T;D
Sift4G	Benign	0.34	T;T;T;T;T;T
Polyphen		0.53, 0.80	.;P;P;P;.;.
Vest4		0.13
MutPred		0.45		.;.;.;Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.49
MPC		0.17
ClinPred		0.39	T
GERP RS		-5.8
Varity_R		0.11
gMVP		0.063

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12453; hg19: chr11-59945745;