10-70153933-T-C
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_020150.5(SAR1A):āc.385A>Gā(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 (ā ).
Frequency
Genomes: š 0.000085 ( 0 hom., cov: 33)
Exomes š: 0.000083 ( 1 hom. )
Consequence
SAR1A
NM_020150.5 missense
NM_020150.5 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 4.66
Genes affected
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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 | UniProt |
---|---|---|---|---|---|---|---|
SAR1A | NM_020150.5 | c.385A>G | p.Ile129Val | missense_variant | 6/7 | ENST00000373241.9 | |
SAR1A | NM_001142648.2 | c.385A>G | p.Ile129Val | missense_variant | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SAR1A | ENST00000373241.9 | c.385A>G | p.Ile129Val | missense_variant | 6/7 | 1 | NM_020150.5 | P1 | |
SAR1A | ENST00000373238.5 | c.385A>G | p.Ile129Val | missense_variant | 6/7 | 2 | P1 | ||
SAR1A | ENST00000373242.6 | c.385A>G | p.Ile129Val | missense_variant | 7/8 | 2 | P1 | ||
SAR1A | ENST00000452767.1 | c.136A>G | p.Ile46Val | missense_variant | 3/4 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000855 AC: 13AN: 152088Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000992 AC: 24AN: 241984Hom.: 0 AF XY: 0.0000611 AC XY: 8AN XY: 130850
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GnomAD4 exome AF: 0.0000827 AC: 120AN: 1450790Hom.: 1 Cov.: 28 AF XY: 0.0000721 AC XY: 52AN XY: 721672
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GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74416
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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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;N
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;B;B;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at