chr11-60383265-C-A

Variant names:

• chr11-60383265-C-A
• NM_021201.5:c.124C>A

Variant summary

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

The NM_021201.5(MS4A7):​c.124C>A​(p.Pro42Thr) 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: MS4A7 NM_021201.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.813
• Publications: 0 publications found

Genes affected

MS4A7 (HGNC:13378): (membrane spanning 4-domains A7) This gene encodes a member of the membrane-spanning 4A gene family, members of which are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns in hematopoietic cells and nonlymphoid tissues. This family member is associated with mature cellular function in the monocytic lineage, and it may be a component of a receptor complex involved in signal transduction. This gene is localized to 11q12, in a cluster of other family members. At least four alternatively spliced transcript variants encoding two distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

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

MS4A6E (HGNC:14285): (membrane spanning 4-domains A6E) 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 11q12.3, 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=0.10137683).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021201.5. 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
	MS4A7	NM_021201.5	MANE Select	c.124C>A	p.Pro42Thr	missense	Exon 2 of 7	NP_067024.1	Q9GZW8-1
	MS4A7	NM_206939.2		c.124C>A	p.Pro42Thr	missense	Exon 2 of 7	NP_996822.1	Q9GZW8-1
	MS4A7	NM_206938.2		c.124C>A	p.Pro42Thr	missense	Exon 2 of 6	NP_996821.1	Q9GZW8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A7	ENST00000300184.8	TSL:1 MANE Select	c.124C>A	p.Pro42Thr	missense	Exon 2 of 7	ENSP00000300184.3	Q9GZW8-1
	MS4A7	ENST00000528808.1	TSL:1	n.270C>A		non_coding_transcript_exon	Exon 2 of 4
	MS4A7	ENST00000899568.1		c.124C>A	p.Pro42Thr	missense	Exon 2 of 7	ENSP00000569627.1

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	0.094
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	1.7
DANN	Benign	0.79
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.81
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.016
Sift	Benign	0.10	T
Sift4G	Benign	0.17	T
Polyphen		0.65	P
Vest4		0.096
MutPred		0.24		Loss of helix (P = 0.0237)
MVP		0.51
MPC		0.039
ClinPred		0.11	T
GERP RS		0.69
Varity_R		0.11
gMVP		0.18
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr11-60150738;