Variant 10-70153933-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000373241.9(SAR1A):c.385A>G(p.Ile129Val) variant causes a missense change. The variant allele was found at a frequency of 0.000083 in 1,602,996 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000083 ( 1 hom. )

Consequence

SAR1A
ENST00000373241.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.66

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053802162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SAR1A	NM_020150.5 linkuse as main transcript	c.385A>G	p.Ile129Val	missense_variant	6/7	ENST00000373241.9	NP_064535.1
SAR1A	NM_001142648.2 linkuse as main transcript	c.385A>G	p.Ile129Val	missense_variant	7/8		NP_001136120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAR1A	ENST00000373241.9 linkuse as main transcript	c.385A>G	p.Ile129Val	missense_variant	6/7	1	NM_020150.5	ENSP00000362338	P1	Q9NR31-1
SAR1A	ENST00000373238.5 linkuse as main transcript	c.385A>G	p.Ile129Val	missense_variant	6/7	2		ENSP00000362335	P1	Q9NR31-1
SAR1A	ENST00000373242.6 linkuse as main transcript	c.385A>G	p.Ile129Val	missense_variant	7/8	2		ENSP00000362339	P1	Q9NR31-1
SAR1A	ENST00000452767.1 linkuse as main transcript	c.136A>G	p.Ile46Val	missense_variant	3/4	5		ENSP00000398165

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000992

AC:

AN:

241984

Hom.:

AF XY:

0.0000611

AC XY:

AN XY:

130850

show subpopulations

Gnomad AFR exome

AF:

0.000189

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000789

Gnomad SAS exome

AF:

0.0000711

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.000510

GnomAD4 exome

AF:

0.0000827

AC:

120

AN:

1450790

Hom.:

Cov.:

AF XY:

0.0000721

AC XY:

AN XY:

721672

show subpopulations

Gnomad4 AFR exome

AF:

0.0000609

Gnomad4 AMR exome

AF:

0.0000234

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000381

Gnomad4 SAS exome

AF:

0.0000476

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000488

Gnomad4 OTH exome

AF:

0.000734

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.000125

ExAC

AF:

0.0000988

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 31, 2022

The c.385A>G (p.I129V) alteration is located in exon 7 (coding exon 5) of the SAR1A gene. This alteration results from a A to G substitution at nucleotide position 385, causing the isoleucine (I) at amino acid position 129 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.041

T;T;T;T

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

.;.;.;D

M_CAP

Benign

0.0075

MetaRNN

Benign

0.054

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.25

N;N;N;N

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.25

N;N;N;N

REVEL

Benign

0.25

Sift

Benign

0.26

T;T;T;T

Sift4G

Benign

0.69

T;T;T;T

Polyphen

0.0010

B;B;B;B

Vest4

0.14

MVP

0.33

MPC

0.58

ClinPred

0.032

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.099

gMVP

0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over