16-625680-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021168.5(RAB40C):​c.342+171T>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: 35)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021168.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB40C	NM_021168.5	MANE Select	c.342+171T>A		intron	N/A	NP_066991.3
	RAB40C	NM_001172663.2		c.342+171T>A		intron	N/A	NP_001166134.1
	RAB40C	NM_001172664.2		c.342+171T>A		intron	N/A	NP_001166135.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB40C	ENST00000248139.8	TSL:1 MANE Select	c.342+171T>A		intron	N/A	ENSP00000248139.3
	RAB40C	ENST00000561781.1	TSL:2	n.67T>A		non_coding_transcript_exon	Exon 1 of 2
	RAB40C	ENST00000535977.5	TSL:5	c.342+171T>A		intron	N/A	ENSP00000438492.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 693644 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 355628

African (AFR) AF: 0.00 AC: 0 AN: 17994

American (AMR) AF: 0.00 AC: 0 AN: 29168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16940

East Asian (EAS) AF: 0.00 AC: 0 AN: 32290

South Asian (SAS) AF: 0.00 AC: 0 AN: 56100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2582

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 472574

Other (OTH) AF: 0.00 AC: 0 AN: 34510

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.19
DANN	Benign	0.51
PhyloP100		-1.3

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;