chr11-60794047-C-A

Variant names:

• chr11-60794047-C-A
• NM_206893.4:c.436C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_206893.4(MS4A10):​c.436C>A​(p.Leu146Ile) 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. 15/22 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: MS4A10 NM_206893.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.270
• Publications: 0 publications found

Genes affected

MS4A10 (HGNC:13368): (membrane spanning 4-domains A10) Most MS4A genes, including MS4A10, encode proteins with at least 4 potential transmembrane domains and N- and C-terminal cytoplasmic domains encoded by distinct exons.[supplied by OMIM, Apr 2004]

LOC105369322 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35659432).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206893.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A10	NM_206893.4	MANE Select	c.436C>A	p.Leu146Ile	missense	Exon 5 of 8	NP_996776.2	Q96PG2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A10	ENST00000308287.2	TSL:1 MANE Select	c.436C>A	p.Leu146Ile	missense	Exon 5 of 8	ENSP00000311862.1	Q96PG2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	0.091
Eigen_PC	Benign	0.0029
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.27
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.10
Sift	Uncertain	0.019	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.64		Gain of ubiquitination at K144 (P = 0.1008)
MVP		0.41
MPC		0.26
ClinPred		0.83	D
GERP RS		1.3
Varity_R		0.11
gMVP		0.14
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

hg19: chr11-60561520;