chr11-60386747-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021201.5(MS4A7):​c.313T>A​(p.Ser105Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,613,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

MS4A7
NM_021201.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.05
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.024539113).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MS4A7NM_021201.5 linkuse as main transcriptc.313T>A p.Ser105Thr missense_variant 4/7 ENST00000300184.8
MS4A7NM_206939.2 linkuse as main transcriptc.313T>A p.Ser105Thr missense_variant 4/7
MS4A7NM_206938.2 linkuse as main transcriptc.178T>A p.Ser60Thr missense_variant 3/6
MS4A7NM_206940.2 linkuse as main transcriptc.178T>A p.Ser60Thr missense_variant 3/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MS4A7ENST00000300184.8 linkuse as main transcriptc.313T>A p.Ser105Thr missense_variant 4/71 NM_021201.5 P1Q9GZW8-1

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152206
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00115
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.0000837
AC:
21
AN:
250970
Hom.:
0
AF XY:
0.0000737
AC XY:
10
AN XY:
135638
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00103
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000561
AC:
82
AN:
1461032
Hom.:
0
Cov.:
29
AF XY:
0.0000495
AC XY:
36
AN XY:
726852
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000428
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00106
GnomAD4 genome
AF:
0.0000656
AC:
10
AN:
152324
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000130
Hom.:
0
Bravo
AF:
0.0000793
ExAC
AF:
0.0000906
AC:
11
Asia WGS
AF:
0.00491
AC:
17
AN:
3478

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 GeneticsJun 19, 2024The c.313T>A (p.S105T) alteration is located in exon 4 (coding exon 3) of the MS4A7 gene. This alteration results from a T to A substitution at nucleotide position 313, causing the serine (S) at amino acid position 105 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
0.13
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
17
DANN
Benign
0.75
DEOGEN2
Benign
0.0018
T;.;.;.;.
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.51
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.54
T;T;.;T;T
M_CAP
Benign
0.0069
T
MetaRNN
Benign
0.025
T;T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
1.5
L;.;.;.;.
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
0.16
N;N;N;N;D
REVEL
Benign
0.081
Sift
Benign
0.83
T;T;T;T;D
Sift4G
Benign
0.17
T;D;D;D;D
Polyphen
1.0
D;P;P;P;.
Vest4
0.31
MVP
0.54
MPC
0.21
ClinPred
0.054
T
GERP RS
1.3
Varity_R
0.086
gMVP
0.30

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2233248; hg19: chr11-60154220; API