NM_021168.5:c.342+171T>C

Variant names:

• chr16-625680-T-C
• rs763014
• NM_021168.5:c.342+171T>C

Variant summary

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

The NM_021168.5(RAB40C):​c.342+171T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 844,800 control chromosomes in the GnomAD database, including 94,700 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 0.47 (17523 hom., cov: 35)
  • Exomes 𝑓: 0.46 (77177 hom.)
• Consequence: RAB40C NM_021168.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 27 publications found

Genes affected

RAB40C (HGNC:18285): (RAB40C, member RAS oncogene family) Predicted to enable GDP binding activity; GTP binding activity; and GTPase activity. Predicted to be involved in protein localization to plasma membrane. Predicted to be located in perinuclear region of cytoplasm. Predicted to be active in endosome; plasma membrane; and synaptic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB40C	NM_021168.5	c.342+171T>C		intron_variant	Intron 4 of 5	ENST00000248139.8	NP_066991.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB40C	ENST00000248139.8	c.342+171T>C		intron_variant	Intron 4 of 5	1	NM_021168.5	ENSP00000248139.3

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72000 AN: 152052 Hom.: 17482 Cov.: 35

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.420

GnomAD4 exome AF: 0.462 AC: 319701 AN: 692630 Hom.: 77177 Cov.: 9 AF XY: 0.468 AC XY: 166047 AN XY: 355154

African (AFR) AF: 0.519 AC: 9336 AN: 17978

American (AMR) AF: 0.537 AC: 15657 AN: 29134

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 6522 AN: 16930

East Asian (EAS) AF: 0.695 AC: 22452 AN: 32284

South Asian (SAS) AF: 0.618 AC: 34659 AN: 56064

European-Finnish (FIN) AF: 0.519 AC: 16349 AN: 31474

Middle Eastern (MID) AF: 0.350 AC: 903 AN: 2580

European-Non Finnish (NFE) AF: 0.421 AC: 198407 AN: 471698

Other (OTH) AF: 0.447 AC: 15416 AN: 34488

GnomAD4 genome AF: 0.474 AC: 72096 AN: 152170 Hom.: 17523 Cov.: 35 AF XY: 0.481 AC XY: 35805 AN XY: 74394

African (AFR) AF: 0.519 AC: 21561 AN: 41528

American (AMR) AF: 0.487 AC: 7455 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1334 AN: 3470

East Asian (EAS) AF: 0.654 AC: 3373 AN: 5156

South Asian (SAS) AF: 0.621 AC: 3000 AN: 4828

European-Finnish (FIN) AF: 0.510 AC: 5403 AN: 10598

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28628 AN: 67966

Other (OTH) AF: 0.426 AC: 902 AN: 2116

Alfa AF: 0.439 Hom.: 15065

Bravo AF: 0.467

Asia WGS AF: 0.669 AC: 2329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.22
DANN	Benign	0.33
PhyloP100		-1.3
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: rs763014; hg19: chr16-675680; COSMIC: COSV50195590; COSMIC: COSV50195590;