Genetic Variant SAR1A:p.Ile131Val (chr10-70153927-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020150.5(SAR1A):c.391A>G(p.Ile131Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,606,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SAR1A
NM_020150.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.99

Publications

1 publications found

Variant links:

Genes affected

SAR1A (HGNC:10534): (secretion associated Ras related GTPase 1A) Predicted to enable GTPase activity. Involved in COPII-coated vesicle cargo loading. Part of COPII vesicle coat. [provided by Alliance of Genome Resources, Apr 2022]

SAR1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15843794).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020150.5. 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
	SAR1A	NM_020150.5	MANE Select	c.391A>G	p.Ile131Val	missense	Exon 6 of 7	NP_064535.1	Q9NR31-1
	SAR1A	NM_001142648.2		c.391A>G	p.Ile131Val	missense	Exon 7 of 8	NP_001136120.1	Q9NR31-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAR1A	ENST00000373241.9	TSL:1 MANE Select	c.391A>G	p.Ile131Val	missense	Exon 6 of 7	ENSP00000362338.4	Q9NR31-1
SAR1A	ENST00000373238.5	TSL:2	c.391A>G	p.Ile131Val	missense	Exon 6 of 7	ENSP00000362335.1	Q9NR31-1
SAR1A	ENST00000373242.6	TSL:2	c.391A>G	p.Ile131Val	missense	Exon 7 of 8	ENSP00000362339.1	Q9NR31-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151630

Hom.:

Cov.:

show subpopulations

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000162

AC:

AN:

246186

AF XY:

0.0000150

show subpopulations

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:

0.0000267

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1455058

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

724074

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33086

American (AMR)

AF:

0.00

AC:

AN:

43830

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26042

East Asian (EAS)

AF:

0.00

AC:

AN:

39412

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85140

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53292

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1108412

Other (OTH)

AF:

0.00

AC:

AN:

60130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151630

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74000

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41202

American (AMR)

AF:

0.00

AC:

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10478

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.047

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.0096

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.48

PhyloP100

5.0

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.46

REVEL

Benign

0.10

Sift

Benign

0.39

Sift4G

Benign

0.73

Polyphen

0.0020

Vest4

0.23

MVP

0.28

MPC

0.59

ClinPred

0.20

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.38

Mutation Taster

=75/25

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over