chr11-60389568-A-T

Variant summary

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

The NM_021201.5(MS4A7):​c.518A>T​(p.Asp173Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

MS4A7
NM_021201.5 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MS4A7NM_021201.5 linkuse as main transcriptc.518A>T p.Asp173Val missense_variant 5/7 ENST00000300184.8
MS4A7NM_206939.2 linkuse as main transcriptc.518A>T p.Asp173Val missense_variant 5/7
MS4A7NM_206938.2 linkuse as main transcriptc.383A>T p.Asp128Val missense_variant 4/6
MS4A7NM_206940.2 linkuse as main transcriptc.383A>T p.Asp128Val missense_variant 4/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MS4A7ENST00000300184.8 linkuse as main transcriptc.518A>T p.Asp173Val missense_variant 5/71 NM_021201.5 P1Q9GZW8-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 05, 2022The c.518A>T (p.D173V) alteration is located in exon 5 (coding exon 4) of the MS4A7 gene. This alteration results from a A to T substitution at nucleotide position 518, causing the aspartic acid (D) at amino acid position 173 to be replaced by a valine (V). 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
0.18
BayesDel_addAF
Benign
-0.054
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.010
T;.;.;.;.
Eigen
Benign
-0.094
Eigen_PC
Benign
-0.16
FATHMM_MKL
Benign
0.55
D
LIST_S2
Benign
0.78
T;T;.;T;T
M_CAP
Benign
0.0093
T
MetaRNN
Uncertain
0.58
D;D;D;D;D
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.4
L;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Benign
0.33
T
PROVEAN
Pathogenic
-5.5
D;D;D;D;D
REVEL
Benign
0.26
Sift
Uncertain
0.0020
D;D;D;D;D
Sift4G
Uncertain
0.0060
D;D;D;D;D
Polyphen
0.98
D;P;P;P;.
Vest4
0.59
MutPred
0.66
Gain of helix (P = 0.0199);.;.;.;.;
MVP
0.30
MPC
0.21
ClinPred
0.87
D
GERP RS
3.7
Varity_R
0.46
gMVP
0.28

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: chr11-60157041; API