chr20-37386120-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_198291.3(SRC):c.296C>T(p.Thr99Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
SRC
NM_198291.3 missense
NM_198291.3 missense
Scores
3
10
5
Clinical Significance
Conservation
PhyloP100: 6.15
Genes affected
SRC (HGNC:11283): (SRC proto-oncogene, non-receptor tyrosine kinase) This gene is highly similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the regulation of embryonic development and cell growth. The protein encoded by this gene is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the malignant progression of colon cancer. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SRC | NM_198291.3 | c.296C>T | p.Thr99Met | missense_variant | 5/14 | ENST00000373578.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SRC | ENST00000373578.7 | c.296C>T | p.Thr99Met | missense_variant | 5/14 | 5 | NM_198291.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461858Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727238
GnomAD4 exome
AF:
AC:
2
AN:
1461858
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
727238
Gnomad4 AFR exome
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Gnomad4 FIN exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
Bravo
AF:
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 | Jan 10, 2023 | The c.296C>T (p.T99M) alteration is located in exon 5 (coding exon 2) of the SRC gene. This alteration results from a C to T substitution at nucleotide position 296, causing the threonine (T) at amino acid position 99 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;D;D;.
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D
Sift4G
Benign
T;T;T;T
Polyphen
D;D;D;.
Vest4
MutPred
Loss of phosphorylation at T99 (P = 0.0376);Loss of phosphorylation at T99 (P = 0.0376);Loss of phosphorylation at T99 (P = 0.0376);Loss of phosphorylation at T99 (P = 0.0376);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at