16-590321-C-T

Variant names:

• chr16-590321-C-T
• rs2035962835
• NM_021168.5:c.30C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_021168.5(RAB40C):​c.30C>T​(p.Ser10Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,437,656 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RAB40C NM_021168.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.24
• Publications: 0 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=3.24 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB40C	NM_021168.5	MANE Select	c.30C>T	p.Ser10Ser	synonymous	Exon 1 of 6	NP_066991.3
	RAB40C	NM_001172663.2		c.30C>T	p.Ser10Ser	synonymous	Exon 2 of 7	NP_001166134.1	Q96S21-1
	RAB40C	NM_001172664.2		c.30C>T	p.Ser10Ser	synonymous	Exon 2 of 7	NP_001166135.1	Q96S21-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB40C	ENST00000248139.8	TSL:1 MANE Select	c.30C>T	p.Ser10Ser	synonymous	Exon 1 of 6	ENSP00000248139.3	Q96S21-1
	RAB40C	ENST00000851113.1		c.30C>T	p.Ser10Ser	synonymous	Exon 1 of 7	ENSP00000521172.1
	RAB40C	ENST00000851112.1		c.30C>T	p.Ser10Ser	synonymous	Exon 1 of 6	ENSP00000521171.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1437656 Hom.: 0 Cov.: 31 AF XY: 0.00000280 AC XY: 2 AN XY: 715146

African (AFR) AF: 0.00 AC: 0 AN: 30362

American (AMR) AF: 0.0000233 AC: 1 AN: 42846

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25352

East Asian (EAS) AF: 0.00 AC: 0 AN: 37072

South Asian (SAS) AF: 0.00 AC: 0 AN: 83800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4592

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102428

Other (OTH) AF: 0.00 AC: 0 AN: 59200

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.94
PhyloP100		3.2
PromoterAI		-0.039	Neutral

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: rs2035962835; hg19: chr16-640321;