11-60715358-C-A

Position:

• chr11-60715358-C-A

Variant summary

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

The NM_031457.2(MS4A8):​c.697C>A​(p.Pro233Thr) 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. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MS4A8 NM_031457.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.37

Genes affected

MS4A8 (HGNC:13380): (membrane spanning 4-domains A8) This gene encodes a member of the membrane-spanning 4A gene family. Members of this 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 11q12.3, among a cluster of family members. [provided by RefSeq, Jul 2008]

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=0.20348656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MS4A8	NM_031457.2	c.697C>A	p.Pro233Thr	missense_variant	7/7	ENST00000300226.7	NP_113645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MS4A8	ENST00000300226.7	c.697C>A	p.Pro233Thr	missense_variant	7/7	1	NM_031457.2	ENSP00000300226.2
MS4A8	ENST00000529752.5	c.644C>A	p.Pro215His	missense_variant	7/7	5		ENSP00000436857.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Dec 19, 2022

The c.697C>A (p.P233T) alteration is located in exon 7 (coding exon 6) of the MS4A8 gene. This alteration results from a C to A substitution at nucleotide position 697, causing the proline (P) at amino acid position 233 to be replaced by a threonine (T). 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	0.075
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.69
Eigen	Benign	0.081
Eigen_PC	Benign	0.049
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.069
Sift	Pathogenic	0.0	D
MutPred		0.15		Loss of stability (P = 0.1318);
MVP		0.40
ClinPred		0.76	D
GERP RS		4.1

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: chr11-60482831;