11-60386730-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_021201.5(MS4A7):​c.296G>A​(p.Gly99Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000754 in 1,613,022 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00080 ( 2 hom. )

Consequence

MS4A7
NM_021201.5 missense

Scores

5
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00
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 Likely_benign. Variant got -4 ACMG points.

BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MS4A7NM_021201.5 linkuse as main transcriptc.296G>A p.Gly99Glu missense_variant 4/7 ENST00000300184.8
MS4A7NM_206939.2 linkuse as main transcriptc.296G>A p.Gly99Glu missense_variant 4/7
MS4A7NM_206938.2 linkuse as main transcriptc.161G>A p.Gly54Glu missense_variant 3/6
MS4A7NM_206940.2 linkuse as main transcriptc.161G>A p.Gly54Glu missense_variant 3/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MS4A7ENST00000300184.8 linkuse as main transcriptc.296G>A p.Gly99Glu missense_variant 4/71 NM_021201.5 P1Q9GZW8-1

Frequencies

GnomAD3 genomes
AF:
0.000361
AC:
55
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000720
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000399
AC:
100
AN:
250872
Hom.:
0
AF XY:
0.000420
AC XY:
57
AN XY:
135602
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000393
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000696
Gnomad OTH exome
AF:
0.000491
GnomAD4 exome
AF:
0.000796
AC:
1162
AN:
1460710
Hom.:
2
Cov.:
29
AF XY:
0.000749
AC XY:
544
AN XY:
726698
show subpopulations
Gnomad4 AFR exome
AF:
0.0000897
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000360
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000977
Gnomad4 OTH exome
AF:
0.000563
GnomAD4 genome
AF:
0.000361
AC:
55
AN:
152312
Hom.:
0
Cov.:
32
AF XY:
0.000389
AC XY:
29
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000720
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000691
Hom.:
0
Bravo
AF:
0.000366
TwinsUK
AF:
0.00162
AC:
6
ALSPAC
AF:
0.000778
AC:
3
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000698
AC:
6
ExAC
AF:
0.000428
AC:
52
EpiCase
AF:
0.000437
EpiControl
AF:
0.000534

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 GeneticsSep 17, 2021The c.296G>A (p.G99E) alteration is located in exon 4 (coding exon 3) of the MS4A7 gene. This alteration results from a G to A substitution at nucleotide position 296, causing the glycine (G) at amino acid position 99 to be replaced by a glutamic acid (E). 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
Pathogenic
0.89
BayesDel_addAF
Uncertain
0.024
T
BayesDel_noAF
Pathogenic
0.24
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.25
T;.;.;.;.
Eigen
Uncertain
0.40
Eigen_PC
Benign
0.17
FATHMM_MKL
Benign
0.63
D
LIST_S2
Benign
0.79
T;T;.;T;T
M_CAP
Benign
0.070
D
MetaRNN
Uncertain
0.62
D;D;D;D;D
MetaSVM
Uncertain
0.19
D
MutationAssessor
Pathogenic
3.8
H;.;.;.;.
MutationTaster
Benign
1.0
D;D;N;N;N
PrimateAI
Benign
0.40
T
PROVEAN
Pathogenic
-7.4
D;D;D;D;D
REVEL
Uncertain
0.45
Sift
Uncertain
0.0020
D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D
Polyphen
1.0
D;D;D;D;.
Vest4
0.80
MVP
0.81
MPC
0.23
ClinPred
0.43
T
GERP RS
3.8
Varity_R
0.92
gMVP
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.21
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.21
Position offset: -13

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: rs36102108; hg19: chr11-60154203; API