rs61739206

Variant names:

• chrX-103500632-G-A
• rs61739206
• NM_080879.3:c.125C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-103500632-G-A
• chrX-103500632-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_080879.3(RAB40A):​c.125C>T​(p.Pro42Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00907 in 1,208,298 control chromosomes in the GnomAD database, including 34 homozygotes. There are 3,419 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.0060 (1 hom., 146 hem., cov: 22)
  • Exomes 𝑓: 0.0094 (33 hom. 3273 hem.)
• Consequence: RAB40A NM_080879.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.50
• Publications: 14 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010980219).
• BS2: High Hemizygotes in GnomAd4 at 146 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.125C>T	p.Pro42Leu	missense	Exon 3 of 3	NP_543155.2	Q8WXH6
	LL0XNC01-250H12.3	NR_188433.1		n.2302G>A		non_coding_transcript_exon	Exon 9 of 9
	LL0XNC01-250H12.3	NR_188435.1		n.2229G>A		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.125C>T	p.Pro42Leu	missense	Exon 3 of 3	ENSP00000305648.1	Q8WXH6
	RAB40A	ENST00000372633.1	TSL:6	c.125C>T	p.Pro42Leu	missense	Exon 1 of 1	ENSP00000361716.1	Q8WXH6
	RAB40A	ENST00000905301.1		c.125C>T	p.Pro42Leu	missense	Exon 4 of 4	ENSP00000575360.1

Frequencies

GnomAD3 genomes AF: 0.00598 AC: 658 AN: 110046 Hom.: 1 Cov.: 22

Gnomad AFR AF: 0.00129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00708

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00252

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00923

Gnomad OTH AF: 0.00682

GnomAD2 exomes AF: 0.00601 AC: 1103 AN: 183513 AF XY: 0.00580

Gnomad AFR exome AF: 0.000836

Gnomad AMR exome AF: 0.00467

Gnomad ASJ exome AF: 0.0130

Gnomad EAS exome AF: 0.0000721

Gnomad FIN exome AF: 0.00225

Gnomad NFE exome AF: 0.00961

Gnomad OTH exome AF: 0.00861

GnomAD4 exome AF: 0.00938 AC: 10301 AN: 1098202 Hom.: 33 Cov.: 33 AF XY: 0.00900 AC XY: 3273 AN XY: 363594

African (AFR) AF: 0.000682 AC: 18 AN: 26403

American (AMR) AF: 0.00497 AC: 175 AN: 35203

Ashkenazi Jewish (ASJ) AF: 0.0117 AC: 226 AN: 19382

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30206

South Asian (SAS) AF: 0.000185 AC: 10 AN: 54146

European-Finnish (FIN) AF: 0.00247 AC: 100 AN: 40533

Middle Eastern (MID) AF: 0.000967 AC: 4 AN: 4136

European-Non Finnish (NFE) AF: 0.0112 AC: 9411 AN: 842101

Other (OTH) AF: 0.00772 AC: 356 AN: 46092

GnomAD4 genome AF: 0.00598 AC: 658 AN: 110096 Hom.: 1 Cov.: 22 AF XY: 0.00451 AC XY: 146 AN XY: 32364

African (AFR) AF: 0.00129 AC: 39 AN: 30242

American (AMR) AF: 0.00708 AC: 74 AN: 10458

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 35 AN: 2628

East Asian (EAS) AF: 0.00 AC: 0 AN: 3496

South Asian (SAS) AF: 0.00 AC: 0 AN: 2405

European-Finnish (FIN) AF: 0.00252 AC: 15 AN: 5953

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.00923 AC: 485 AN: 52531

Other (OTH) AF: 0.00673 AC: 10 AN: 1486

Alfa AF: 0.00608 Hom.: 75

Bravo AF: 0.00639

ESP6500AA AF: 0.00156 AC: 6

ESP6500EA AF: 0.0120 AC: 81

ExAC AF: 0.00593 AC: 720

EpiCase AF: 0.00720

EpiControl AF: 0.00937

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.5
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.048	D
Polyphen		1.0	D
Vest4		0.21
MVP		0.94
MPC		1.9
ClinPred		0.075	T
GERP RS		-0.71
Varity_R		0.24
gMVP		0.75
Mutation Taster		=100/0	polymorphism (auto)

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: rs61739206; hg19: chrX-102755560;