rs181581015

Variant summary

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

The NM_015065.3(EXPH5):​c.5605G>C​(p.Gly1869Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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 š‘“: 6.9e-7 ( 0 hom. )

Consequence

EXPH5
NM_015065.3 missense

Scores

16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.645
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]

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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=0.020539701).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EXPH5NM_015065.3 linkc.5605G>C p.Gly1869Arg missense_variant Exon 6 of 6 ENST00000265843.9 NP_055880.2 Q8NEV8-1Q149M6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EXPH5ENST00000265843.9 linkc.5605G>C p.Gly1869Arg missense_variant Exon 6 of 6 1 NM_015065.3 ENSP00000265843.4 Q8NEV8-1
EXPH5ENST00000525344.5 linkc.5584G>C p.Gly1862Arg missense_variant Exon 7 of 7 1 ENSP00000432546.1 Q8NEV8-2
EXPH5ENST00000526312.5 linkc.*177G>C downstream_gene_variant 1 ENSP00000432683.1 E9PPH6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1454476
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
723322
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
0.018
DANN
Benign
0.16
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.062
N
M_CAP
Benign
0.0043
T
MetaRNN
Benign
0.021
T;T
MetaSVM
Benign
-0.92
T
PrimateAI
Benign
0.25
T
PROVEAN
Benign
2.5
N;N
REVEL
Benign
0.024
Sift
Benign
1.0
T;T
Sift4G
Benign
0.79
T;T
Vest4
0.053
MutPred
0.19
Loss of ubiquitination at K1871 (P = 0.0224);.;
MVP
0.040
MPC
0.041
ClinPred
0.071
T
GERP RS
-0.87
gMVP
0.061

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: chr11-108380629; API