11-108509396-GA-GAAAAAAAAAA

Variant names:

• chr11-108509396-G-GAAAAAAAAA
• rs201174655
• NM_015065.3:c.*140_*141insTTTTTTTTT

Variant summary

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

The NM_015065.3(EXPH5):​c.*140_*141insTTTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EXPH5 NM_015065.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774

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]

LOC112267909 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXPH5	NM_015065.3	c.*140_*141insTTTTTTTTT		3_prime_UTR_variant	Exon 6 of 6	ENST00000265843.9	NP_055880.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXPH5	ENST00000265843	c.*140_*141insTTTTTTTTT		3_prime_UTR_variant	Exon 6 of 6	1	NM_015065.3	ENSP00000265843.4
EXPH5	ENST00000525344	c.*140_*141insTTTTTTTTT		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000432546.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 8

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201174655; hg19: chr11-108380123;