chr10-95414595-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001034954.3(SORBS1):ā€‹c.709A>Gā€‹(p.Thr237Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0683 in 1,605,834 control chromosomes in the GnomAD database, including 6,871 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T237M) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.12 ( 2113 hom., cov: 31)
Exomes š‘“: 0.063 ( 4758 hom. )

Consequence

SORBS1
NM_001034954.3 missense

Scores

3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.02
Variant links:
Genes affected
SORBS1 (HGNC:14565): (sorbin and SH3 domain containing 1) This gene encodes a CBL-associated protein which functions in the signaling and stimulation of insulin. Mutations in this gene may be associated with human disorders of insulin resistance. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0034773946).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SORBS1NM_001034954.3 linkuse as main transcriptc.709A>G p.Thr237Ala missense_variant 9/33 ENST00000371247.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SORBS1ENST00000371247.7 linkuse as main transcriptc.709A>G p.Thr237Ala missense_variant 9/335 NM_001034954.3 P3Q9BX66-1

Frequencies

GnomAD3 genomes
AF:
0.123
AC:
18736
AN:
151882
Hom.:
2111
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.298
Gnomad AMI
AF:
0.0274
Gnomad AMR
AF:
0.0789
Gnomad ASJ
AF:
0.0854
Gnomad EAS
AF:
0.123
Gnomad SAS
AF:
0.138
Gnomad FIN
AF:
0.00896
Gnomad MID
AF:
0.0764
Gnomad NFE
AF:
0.0477
Gnomad OTH
AF:
0.112
GnomAD3 exomes
AF:
0.0822
AC:
20047
AN:
243874
Hom.:
1468
AF XY:
0.0817
AC XY:
10736
AN XY:
131484
show subpopulations
Gnomad AFR exome
AF:
0.304
Gnomad AMR exome
AF:
0.0567
Gnomad ASJ exome
AF:
0.0932
Gnomad EAS exome
AF:
0.128
Gnomad SAS exome
AF:
0.145
Gnomad FIN exome
AF:
0.0120
Gnomad NFE exome
AF:
0.0465
Gnomad OTH exome
AF:
0.0732
GnomAD4 exome
AF:
0.0625
AC:
90870
AN:
1453834
Hom.:
4758
Cov.:
32
AF XY:
0.0643
AC XY:
46464
AN XY:
722148
show subpopulations
Gnomad4 AFR exome
AF:
0.311
Gnomad4 AMR exome
AF:
0.0586
Gnomad4 ASJ exome
AF:
0.0903
Gnomad4 EAS exome
AF:
0.119
Gnomad4 SAS exome
AF:
0.141
Gnomad4 FIN exome
AF:
0.0119
Gnomad4 NFE exome
AF:
0.0475
Gnomad4 OTH exome
AF:
0.0840
GnomAD4 genome
AF:
0.123
AC:
18771
AN:
152000
Hom.:
2113
Cov.:
31
AF XY:
0.121
AC XY:
9001
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.298
Gnomad4 AMR
AF:
0.0788
Gnomad4 ASJ
AF:
0.0854
Gnomad4 EAS
AF:
0.124
Gnomad4 SAS
AF:
0.139
Gnomad4 FIN
AF:
0.00896
Gnomad4 NFE
AF:
0.0477
Gnomad4 OTH
AF:
0.114
Alfa
AF:
0.0869
Hom.:
669
Bravo
AF:
0.135
TwinsUK
AF:
0.0550
AC:
204
ALSPAC
AF:
0.0540
AC:
208
ESP6500AA
AF:
0.305
AC:
1344
ESP6500EA
AF:
0.0516
AC:
444
ExAC
AF:
0.0856
AC:
10392
Asia WGS
AF:
0.143
AC:
495
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.65
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
18
DANN
Benign
0.71
DEOGEN2
Benign
0.17
.;.;.;T;T;.;.;.
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.10
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.86
D;D;D;T;.;.;T;T
MetaRNN
Benign
0.0035
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.2
M;.;M;M;M;M;.;.
MutationTaster
Benign
0.98
P;P;P;P;P;P;P;P;P;P;P;P;P;P
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-1.7
N;N;N;N;N;N;N;N
REVEL
Benign
0.034
Sift
Uncertain
0.0080
D;D;D;D;D;D;T;D
Sift4G
Benign
0.57
T;T;T;T;T;T;T;T
Polyphen
0.79
P;B;P;B;B;P;P;.
Vest4
0.12
MPC
0.19
ClinPred
0.012
T
GERP RS
1.8
Varity_R
0.067
gMVP
0.16

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: rs2281939; hg19: chr10-97174352; COSMIC: COSV53357011; COSMIC: COSV53357011; API