rs977660903

Variant names:

• chr8-17247316-C-A
• NM_152415.3:c.72C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-17247316-C-A
• chr8-17247316-C-G
• chr8-17247316-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152415.3(VPS37A):​c.72C>A​(p.Ser24Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,410,576 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: VPS37A NM_152415.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.584

Genes affected

VPS37A (HGNC:24928): (VPS37A subunit of ESCRT-I) This gene belongs to the VPS37 family, and encodes a component of the ESCRT-I (endosomal sorting complex required for transport I) protein complex, required for the sorting of ubiquitinated transmembrane proteins into internal vesicles of multivesicular bodies. Expression of this gene is downregulated in hepatocellular carcinoma, and mutations in this gene are associated with autosomal recessive spastic paraplegia-53. A related pseudogene has been identified on chromosome 5. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28197652).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS37A	NM_152415.3	c.72C>A	p.Ser24Arg	missense_variant	Exon 1 of 12	ENST00000324849.9	NP_689628.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS37A	ENST00000324849.9	c.72C>A	p.Ser24Arg	missense_variant	Exon 1 of 12	1	NM_152415.3	ENSP00000318629.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1410576 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 696948

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: 9.21e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T;T;.;T
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.22
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.88	D;D;T;D
M_CAP	Pathogenic	0.39	D
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.3	M;.;M;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.6	N;D;N;D
REVEL	Benign	0.27
Sift	Uncertain	0.0080	D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		1.0	D;.;D;.
Vest4		0.28
MutPred		0.27		Gain of MoRF binding (P = 0.0097);Gain of MoRF binding (P = 0.0097);Gain of MoRF binding (P = 0.0097);Gain of MoRF binding (P = 0.0097);
MVP		0.17
MPC		0.045
ClinPred		0.98	D
GERP RS		2.2
Varity_R		0.63
gMVP		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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-17104825;