chr11-60337918-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_139249.4(MS4A6E):ā€‹c.325G>Cā€‹(p.Asp109His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

MS4A6E
NM_139249.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.130
Variant links:
Genes affected
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.40730712).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MS4A6ENM_139249.4 linkuse as main transcriptc.325G>C p.Asp109His missense_variant 3/5 ENST00000684409.1
MS4A6ENR_170614.1 linkuse as main transcriptn.493G>C non_coding_transcript_exon_variant 3/6
MS4A6ENR_170616.1 linkuse as main transcriptn.613G>C non_coding_transcript_exon_variant 4/6
MS4A6ENR_170615.1 linkuse as main transcriptn.541+72G>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MS4A6EENST00000684409.1 linkuse as main transcriptc.325G>C p.Asp109His missense_variant 3/5 NM_139249.4 P1
MS4A6EENST00000300182.8 linkuse as main transcriptc.325G>C p.Asp109His missense_variant 2/41 P1
MS4A6EENST00000532756.1 linkuse as main transcriptc.250G>C p.Asp84His missense_variant, NMD_transcript_variant 2/54
MS4A6EENST00000530509.1 linkuse as main transcriptc.*112+72G>C intron_variant, NMD_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
33
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

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 GeneticsNov 06, 2023The c.325G>C (p.D109H) alteration is located in exon 2 (coding exon 2) of the MS4A6E gene. This alteration results from a G to C substitution at nucleotide position 325, causing the aspartic acid (D) at amino acid position 109 to be replaced by a histidine (H). 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
0.20
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
14
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0083
T
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.69
FATHMM_MKL
Benign
0.019
N
LIST_S2
Benign
0.64
T
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.41
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.26
T
PROVEAN
Uncertain
-3.5
D
REVEL
Benign
0.039
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.012
D
Polyphen
0.99
D
Vest4
0.18
MutPred
0.63
Loss of loop (P = 0.0128);
MVP
0.093
MPC
0.26
ClinPred
0.62
D
GERP RS
0.91
Varity_R
0.26
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs1227810109; hg19: chr11-60105391; API