rs1433230982

Variant names:

• chr16-590302-A-C
• NM_021168.5:c.11A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-590302-A-C
• chr16-590302-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021168.5(RAB40C):​c.11A>C​(p.Gln4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,395,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q4R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: RAB40C NM_021168.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24603418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB40C	NM_021168.5	c.11A>C	p.Gln4Pro	missense_variant	Exon 1 of 6	ENST00000248139.8	NP_066991.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB40C	ENST00000248139.8	c.11A>C	p.Gln4Pro	missense_variant	Exon 1 of 6	1	NM_021168.5	ENSP00000248139.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1395534 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 694548

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Benign	0.80
DEOGEN2	Benign	0.0027	T;T;.;T;.;T;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	T;.;T;.;T;T;.
M_CAP	Pathogenic	0.44	D
MetaRNN	Benign	0.25	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	.;N;.;N;.;N;N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.080	N;N;N;N;N;N;N
REVEL	Uncertain	0.42
Sift	Benign	0.32	T;T;T;T;T;T;T
Sift4G	Benign	0.29	T;T;T;T;T;T;T
Polyphen		0.0	.;B;.;B;.;B;B
Vest4		0.59, 0.60, 0.60, 0.57
MutPred		0.27		Gain of glycosylation at Q4 (P = 0.048);Gain of glycosylation at Q4 (P = 0.048);Gain of glycosylation at Q4 (P = 0.048);Gain of glycosylation at Q4 (P = 0.048);Gain of glycosylation at Q4 (P = 0.048);Gain of glycosylation at Q4 (P = 0.048);Gain of glycosylation at Q4 (P = 0.048);
MVP		0.76
MPC		2.2
ClinPred		0.71	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.14
gMVP		0.77

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: chr16-640302;