chr11-60429699-C-T

Variant names:

• chr11-60429699-C-T
• NM_023945.3:c.25C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_023945.3(MS4A5):​c.25C>T​(p.Pro9Ser) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MS4A5 NM_023945.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.80
• Publications: 0 publications found

Genes affected

MS4A5 (HGNC:13374): (membrane spanning 4-domains A5) 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. Though this member is not expressed in hematopoietic cells specifically, it may be involved in signal transduction like many of its related family members. The gene encoding this protein is localized to 11q12, among a cluster of family members. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1467852).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023945.3. 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
	MS4A5	NM_023945.3	MANE Select	c.25C>T	p.Pro9Ser	missense	Exon 1 of 5	NP_076434.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A5	ENST00000300190.7	TSL:1 MANE Select	c.25C>T	p.Pro9Ser	missense	Exon 1 of 5	ENSP00000300190.2	Q9H3V2
	MS4A5	ENST00000531403.5	TSL:3	n.25C>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000435192.1	A0A0B4J228
	MS4A5	ENST00000533885.5	TSL:4	n.25C>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000435330.1	E9PKT5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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	0.22
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.035
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.8
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.082
Sift	Benign	0.062	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.14
MutPred		0.56		Gain of sheet (P = 0.0149)
MVP		0.014
MPC		0.13
ClinPred		0.96	D
GERP RS		3.8
PromoterAI		-0.0055	Neutral
Varity_R		0.063
gMVP		0.26
Mutation Taster		=96/4	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: chr11-60197172;