11-60339905-T-C

Variant names:

• chr11-60339905-T-C
• NM_139249.4:c.394T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139249.4(MS4A6E):​c.394T>C​(p.Phe132Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F132I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MS4A6E NM_139249.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14185011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A6E	NM_139249.4	c.394T>C	p.Phe132Leu	missense_variant	Exon 4 of 5	ENST00000684409.1	NP_640342.1
MS4A6E	NR_170614.1	n.562T>C		non_coding_transcript_exon_variant	Exon 4 of 6
MS4A6E	NR_170616.1	n.682T>C		non_coding_transcript_exon_variant	Exon 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A6E	ENST00000684409.1	c.394T>C	p.Phe132Leu	missense_variant	Exon 4 of 5		NM_139249.4	ENSP00000507799.1
MS4A6E	ENST00000300182.8	c.394T>C	p.Phe132Leu	missense_variant	Exon 3 of 4	1		ENSP00000300182.4
MS4A6E	ENST00000532756.1	n.319T>C		non_coding_transcript_exon_variant	Exon 3 of 5	4		ENSP00000432963.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461588 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727108

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.64
DANN	Benign	0.16
DEOGEN2	Benign	0.00055	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0050	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.49	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.066
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.036	B
Vest4		0.17
MutPred		0.73		Loss of catalytic residue at F132 (P = 0.0371);
MVP		0.068
MPC		0.085
ClinPred		0.077	T
GERP RS		-0.68
Varity_R		0.044
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr11-60107378;