NM_017966.5:c.-6-143T>C

Variant names:

• chr11-61138978-A-G
• rs508970
• NM_017966.5:c.-6-143T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017966.5(VPS37C):​c.-6-143T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 726,456 control chromosomes in the GnomAD database, including 142,491 homozygotes. 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: 𝑓 0.65 (34260 hom., cov: 31)
  • Exomes 𝑓: 0.59 (108231 hom.)
• Consequence: VPS37C NM_017966.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017966.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS37C	NM_017966.5	MANE Select	c.-6-143T>C		intron	N/A	NP_060436.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS37C	ENST00000301765.10	TSL:1 MANE Select	c.-6-143T>C		intron	N/A	ENSP00000301765.5
	VPS37C	ENST00000865214.1		c.-149T>C		5_prime_UTR	Exon 1 of 4	ENSP00000535273.1
	VPS37C	ENST00000865212.1		c.-6-143T>C		intron	N/A	ENSP00000535271.1

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99236 AN: 151922 Hom.: 34205 Cov.: 31

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.616

GnomAD4 exome AF: 0.592 AC: 340165 AN: 574416 Hom.: 108231 AF XY: 0.602 AC XY: 181743 AN XY: 302070

African (AFR) AF: 0.834 AC: 13072 AN: 15672

American (AMR) AF: 0.720 AC: 20801 AN: 28904

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 8955 AN: 16170

East Asian (EAS) AF: 0.999 AC: 31900 AN: 31944

South Asian (SAS) AF: 0.804 AC: 43938 AN: 54656

European-Finnish (FIN) AF: 0.601 AC: 19000 AN: 31634

Middle Eastern (MID) AF: 0.526 AC: 2021 AN: 3840

European-Non Finnish (NFE) AF: 0.506 AC: 182586 AN: 361196

Other (OTH) AF: 0.589 AC: 17892 AN: 30400

GnomAD4 genome AF: 0.653 AC: 99354 AN: 152040 Hom.: 34260 Cov.: 31 AF XY: 0.662 AC XY: 49149 AN XY: 74298

African (AFR) AF: 0.829 AC: 34397 AN: 41482

American (AMR) AF: 0.667 AC: 10195 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1953 AN: 3468

East Asian (EAS) AF: 0.997 AC: 5152 AN: 5170

South Asian (SAS) AF: 0.835 AC: 4002 AN: 4792

European-Finnish (FIN) AF: 0.626 AC: 6632 AN: 10590

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35112 AN: 67946

Other (OTH) AF: 0.621 AC: 1311 AN: 2110

Alfa AF: 0.600 Hom.: 3723

Bravo AF: 0.661

Asia WGS AF: 0.911 AC: 3167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.47
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs508970; hg19: chr11-60906450;