11-61138978-A-T

Position:

• chr11-61138978-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017966.5(VPS37C):​c.-6-143T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 31)
• Consequence: VPS37C NM_017966.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128

Genes affected

VPS37C (HGNC:26097): (VPS37C subunit of ESCRT-I) VPS37C is a subunit of ESCRT-I (endosomal sorting complex required for transport I), a complex in the class E vacuolar protein sorting (VPS) pathway required for sorting ubiquitinated transmembrane proteins into internal vesicles of multivesicular bodies (Eastman et al., 2005 [PubMed 15509564]).[supplied by OMIM, Mar 2008]

ACMG classification

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 (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS37C	NM_017966.5	c.-6-143T>A		intron_variant		ENST00000301765.10	NP_060436.4
VPS37C	XM_005274077.4	c.-6-143T>A		intron_variant			XP_005274134.1
VPS37C	XM_047427178.1	c.-6-143T>A		intron_variant			XP_047283134.1
VPS37C	XM_047427179.1	c.-6-143T>A		intron_variant			XP_047283135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS37C	ENST00000301765.10	c.-6-143T>A		intron_variant		1	NM_017966.5	ENSP00000301765	P1
VPS37C	ENST00000538036.1	c.-6-143T>A		intron_variant		2		ENSP00000446013
VPS37C	ENST00000535818.1	n.226-143T>A		intron_variant, non_coding_transcript_variant		2
VPS37C	ENST00000536000.1	n.64-143T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs508970; hg19: chr11-60906450;