dbSNP rs115867994: EXPH5:p.Arg1875Ser (chr11-108509882-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015065.3(EXPH5):c.5625G>T(p.Arg1875Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

EXPH5
NM_015065.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.238

Variant links:

Genes affected

EXPH5 (HGNC:30578): (exophilin 5) The protein encoded by this gene is a member of the synaptotagmin-like protein (Slp) family lacking a C2 domain. It contains an N-terminal synaptotagmin-like homology domain (SHD), and is a ras-related protein Rab-27B effector protein. This protein is thought to be involved in exosome secretion and intracellular vesicle trafficking. Reduced expression of this gene results in keratin filament defects. Mutations in this gene have been associated with some cases of epidermolysis bullosa, an inherited skin fragility disorder. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

EXPH5 links:

LOC112267909 (HGNC:):

LOC112267909 links:

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ACMG classification

Classification made for transcript

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=0.09797123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXPH5	NM_015065.3 link	c.5625G>T	p.Arg1875Ser	missense_variant	Exon 6 of 6	ENST00000265843.9	NP_055880.2	Q8NEV8-1Q149M6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EXPH5	ENST00000265843.9 link	c.5625G>T	p.Arg1875Ser	missense_variant	Exon 6 of 6	1	NM_015065.3	ENSP00000265843.4	Q8NEV8-1
EXPH5	ENST00000525344.5 link	c.5604G>T	p.Arg1868Ser	missense_variant	Exon 7 of 7	1		ENSP00000432546.1	Q8NEV8-2
EXPH5	ENST00000526312.5 link	c.*197G>T		downstream_gene_variant		1		ENSP00000432683.1	E9PPH6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245786

Hom.:

AF XY:

0.00000753

AC XY:

AN XY:

132836

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000550

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1456842

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724528

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.069

M_CAP

Benign

0.0087

MetaRNN

Benign

0.098

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.048

Sift

Uncertain

0.0030

D;D

Sift4G

Benign

0.25

T;T

Vest4

0.22

MutPred

0.48

Loss of MoRF binding (P = 0.0157);.;

MVP

0.12

MPC

0.058

ClinPred

0.32

GERP RS

2.3

gMVP

0.25

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over