7-140407726-A-G

Variant names:

• chr7-140407726-A-G
• rs367821693
• NM_001008749.3:c.80A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001008749.3(RAB19):​c.80A>G​(p.Asn27Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000756 in 1,613,910 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000079 (1 hom.)
• Consequence: RAB19 NM_001008749.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.31
• Publications: 0 publications found

Genes affected

RAB19 (HGNC:19982): (RAB19, member RAS oncogene family) Predicted to enable GTPase activity. Predicted to be involved in autophagosome assembly and intracellular protein transport. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2860845).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008749.3. 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
	RAB19	NM_001008749.3	MANE Select	c.80A>G	p.Asn27Ser	missense	Exon 2 of 4	NP_001008749.2	A4D1S5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB19	ENST00000537763.6	TSL:2 MANE Select	c.80A>G	p.Asn27Ser	missense	Exon 2 of 4	ENSP00000440167.1	A4D1S5-1
	RAB19	ENST00000356407.3	TSL:1	c.80A>G	p.Asn27Ser	missense	Exon 1 of 3	ENSP00000348778.3	A4D1S5-1
	RAB19	ENST00000897796.1		c.80A>G	p.Asn27Ser	missense	Exon 2 of 4	ENSP00000567855.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152032 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000755 AC: 19 AN: 251494 AF XY: 0.0000736

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000787 AC: 115 AN: 1461878 Hom.: 1 Cov.: 32 AF XY: 0.0000770 AC XY: 56 AN XY: 727242

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000890 AC: 99 AN: 1112000

Other (OTH) AF: 0.0000497 AC: 3 AN: 60394

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152032 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74224

African (AFR) AF: 0.0000242 AC: 1 AN: 41386

American (AMR) AF: 0.00 AC: 0 AN: 15238

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000116 Hom.: 0

Bravo AF: 0.0000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

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	0.095
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	-0.28	N
PhyloP100		5.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.34
Sift	Benign	0.14	T
Sift4G	Uncertain	0.055	T
Polyphen		0.93	P
Vest4		0.50
MVP		0.55
MPC		0.54
ClinPred		0.13	T
GERP RS		4.8
PromoterAI		-0.015	Neutral
Varity_R		0.11
gMVP		0.19
Mutation Taster		=71/29	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: rs367821693; hg19: chr7-140107526;