5-134606975-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3

The NM_016103.4(SAR1B):​c.572G>T​(p.Arg191Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

SAR1B
NM_016103.4 missense

Scores

9
8
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.91
Variant links:
Genes affected
SAR1B (HGNC:10535): (secretion associated Ras related GTPase 1B) The protein encoded by this gene is a small GTPase that acts as a homodimer. The encoded protein is activated by the guanine nucleotide exchange factor PREB and is involved in protein transport from the endoplasmic reticulum to the Golgi. This protein is part of the COPII coat complex. Defects in this gene are a cause of chylomicron retention disease (CMRD), also known as Anderson disease (ANDD). Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Mar 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM1
In a chain GTP-binding protein SAR1b (size 197) in uniprot entity SAR1B_HUMAN there are 11 pathogenic changes around while only 1 benign (92%) in NM_016103.4
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.827

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SAR1BNM_016103.4 linkc.572G>T p.Arg191Leu missense_variant Exon 7 of 7 ENST00000402673.7 NP_057187.1 Q9Y6B6
SAR1BNM_001033503.3 linkc.572G>T p.Arg191Leu missense_variant Exon 8 of 8 NP_001028675.1 Q9Y6B6
SAR1BXM_047417257.1 linkc.572G>T p.Arg191Leu missense_variant Exon 7 of 7 XP_047273213.1
SAR1BXM_047417258.1 linkc.368G>T p.Arg123Leu missense_variant Exon 5 of 5 XP_047273214.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SAR1BENST00000402673.7 linkc.572G>T p.Arg191Leu missense_variant Exon 7 of 7 1 NM_016103.4 ENSP00000385432.2 Q9Y6B6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.82
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.27
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.39
T;.;.;T;.
Eigen
Pathogenic
0.70
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
.;.;.;D;D
M_CAP
Uncertain
0.15
D
MetaRNN
Pathogenic
0.83
D;D;D;D;D
MetaSVM
Uncertain
-0.14
T
MutationAssessor
Pathogenic
2.9
M;.;.;M;.
PrimateAI
Uncertain
0.73
T
PROVEAN
Pathogenic
-5.2
D;D;D;D;D
REVEL
Uncertain
0.59
Sift
Uncertain
0.0010
D;D;D;D;D
Sift4G
Uncertain
0.033
D;D;D;D;D
Polyphen
0.98
D;.;.;D;.
Vest4
0.80
MutPred
0.56
Loss of MoRF binding (P = 6e-04);.;.;Loss of MoRF binding (P = 6e-04);.;
MVP
0.88
MPC
0.82
ClinPred
0.99
D
GERP RS
4.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.82
gMVP
0.65

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.

Other links and lift over

dbSNP: rs200409139; hg19: chr5-133942665; API