16-627598-G-T

Variant names:

• chr16-627598-G-T
• rs545420040
• NM_021168.5:c.822G>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_021168.5(RAB40C):​c.822G>T​(p.Ser274Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,595,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: RAB40C NM_021168.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.91
• Publications: 2 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-627598-G-T is Benign according to our data. Variant chr16-627598-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 747292.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.91 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.822G>T	p.Ser274Ser	synonymous	Exon 6 of 6	NP_066991.3
	RAB40C	NM_001172663.2		c.822G>T	p.Ser274Ser	synonymous	Exon 7 of 7	NP_001166134.1	Q96S21-1
	RAB40C	NM_001172664.2		c.822G>T	p.Ser274Ser	synonymous	Exon 7 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.822G>T	p.Ser274Ser	synonymous	Exon 6 of 6	ENSP00000248139.3	Q96S21-1
	RAB40C	ENST00000851113.1		c.1002G>T	p.Ser334Ser	synonymous	Exon 7 of 7	ENSP00000521172.1
	RAB40C	ENST00000851112.1		c.834G>T	p.Ser278Ser	synonymous	Exon 6 of 6	ENSP00000521171.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000298 AC: 7 AN: 235246 AF XY: 0.0000315

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000122

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000104 AC: 15 AN: 1443704 Hom.: 0 Cov.: 31 AF XY: 0.00000978 AC XY: 7 AN XY: 715894

African (AFR) AF: 0.00 AC: 0 AN: 33072

American (AMR) AF: 0.000116 AC: 5 AN: 43262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24954

East Asian (EAS) AF: 0.00 AC: 0 AN: 39418

South Asian (SAS) AF: 0.0000475 AC: 4 AN: 84276

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5650

European-Non Finnish (NFE) AF: 0.00000545 AC: 6 AN: 1101240

Other (OTH) AF: 0.00 AC: 0 AN: 59504

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152220 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74366

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.53
DANN	Benign	0.58
PhyloP100		-3.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs545420040; hg19: chr16-677598;