rs762648669

Variant names:

• chrX-103500594-T-C
• rs762648669
• NM_080879.3:c.163A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_080879.3(RAB40A):​c.163A>G​(p.Thr55Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000061 in 1,098,220 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.000061 (0 hom. 20 hem.)
  • Failed GnomAD Quality Control
• Consequence: RAB40A NM_080879.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.32
• Publications: 0 publications found

Genes affected

RAB40A (HGNC:18283): (RAB40A, member RAS oncogene family) This gene encodes a member of the Rab40 subfamily of Rab small GTP-binding proteins that contains a C-terminal suppressors of cytokine signaling box. [provided by RefSeq, Apr 2010]

LL0XNC01-250H12.3 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3989887).
• BS2: High Hemizygotes in GnomAdExome4 at 20 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080879.3. 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
	RAB40A	NM_080879.3	MANE Select	c.163A>G	p.Thr55Ala	missense	Exon 3 of 3	NP_543155.2	Q8WXH6
	LL0XNC01-250H12.3	NR_188433.1		n.2264T>C		non_coding_transcript_exon	Exon 9 of 9
	LL0XNC01-250H12.3	NR_188435.1		n.2191T>C		non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB40A	ENST00000304236.2	TSL:2 MANE Select	c.163A>G	p.Thr55Ala	missense	Exon 3 of 3	ENSP00000305648.1	Q8WXH6
	RAB40A	ENST00000372633.1	TSL:6	c.163A>G	p.Thr55Ala	missense	Exon 1 of 1	ENSP00000361716.1	Q8WXH6
	RAB40A	ENST00000905301.1		c.163A>G	p.Thr55Ala	missense	Exon 4 of 4	ENSP00000575360.1

Frequencies

GnomAD3 genomes AF: 0.00000905 AC: 1 AN: 110557 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000190

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000163 AC: 3 AN: 183508 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000366

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000610 AC: 67 AN: 1098220 Hom.: 0 Cov.: 33 AF XY: 0.0000550 AC XY: 20 AN XY: 363592

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.00 AC: 0 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19384

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54147

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.0000784 AC: 66 AN: 842114

Other (OTH) AF: 0.0000217 AC: 1 AN: 46093

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000905 AC: 1 AN: 110557 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 32787

African (AFR) AF: 0.00 AC: 0 AN: 30387

American (AMR) AF: 0.00 AC: 0 AN: 10508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2631

East Asian (EAS) AF: 0.00 AC: 0 AN: 3523

South Asian (SAS) AF: 0.00 AC: 0 AN: 2469

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6002

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.0000190 AC: 1 AN: 52659

Other (OTH) AF: 0.00 AC: 0 AN: 1466

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.40	T
MetaSVM	Uncertain	-0.053	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.3
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.049	D
Polyphen		1.0	D
Vest4		0.23
MutPred		0.64		Gain of ubiquitination at K52 (P = 0.102)
MVP		0.97
MPC		1.8
ClinPred		0.92	D
GERP RS		0.85
Varity_R		0.46
gMVP		0.68
Mutation Taster		=100/0	polymorphism

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: rs762648669; hg19: chrX-102755522;