NM_001025300.3:c.486C>T

Variant names:

• chr18-8609925-C-T
• rs376808169
• NM_001025300.3:c.486C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001025300.3(RAB12):​c.486C>T​(p.Thr162Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,457,198 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: RAB12 NM_001025300.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.103
• Publications: 0 publications found

Genes affected

RAB12 (HGNC:31332): (RAB12, member RAS oncogene family) Enables GDP binding activity. Predicted to be involved in several processes, including cellular response to insulin stimulus; endosome to lysosome transport; and secretion by cell. Predicted to act upstream of or within cellular response to interferon-gamma. Predicted to be located in lysosome; phagocytic vesicle; and recycling endosome membrane. Predicted to be active in Golgi apparatus; cytoplasmic vesicle; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 18-8609925-C-T is Benign according to our data. Variant chr18-8609925-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3429083.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.103 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025300.3. 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
	RAB12	NM_001025300.3	MANE Select	c.486C>T	p.Thr162Thr	synonymous	Exon 1 of 6	NP_001020471.3	A0A3B3ITT1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB12	ENST00000649141.2	MANE Select	c.486C>T	p.Thr162Thr	synonymous	Exon 1 of 6	ENSP00000497886.1	A0A3B3ITT1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1457198 Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3 AN XY: 724910

African (AFR) AF: 0.00 AC: 0 AN: 33184

American (AMR) AF: 0.00 AC: 0 AN: 44306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26044

East Asian (EAS) AF: 0.00 AC: 0 AN: 39358

South Asian (SAS) AF: 0.00 AC: 0 AN: 85682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1110248

Other (OTH) AF: 0.00 AC: 0 AN: 60232

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	12
DANN	Benign	0.97
PhyloP100		-0.10
PromoterAI		-0.046	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: rs376808169; hg19: chr18-8609923;