rs12329503

Variant names:

• chr20-37378728-T-C
• rs12329503
• NM_198291.3:c.-172-3891T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198291.3(SRC):​c.-172-3891T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,982 control chromosomes in the GnomAD database, including 8,767 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (8767 hom., cov: 30)
• Consequence: SRC NM_198291.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRC	NM_198291.3	c.-172-3891T>C		intron_variant	Intron 2 of 13	ENST00000373578.7	NP_938033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRC	ENST00000373578.7	c.-172-3891T>C		intron_variant	Intron 2 of 13	5	NM_198291.3	ENSP00000362680.2

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44499 AN: 151862 Hom.: 8739 Cov.: 30

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.284

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.293 AC: 44567 AN: 151982 Hom.: 8767 Cov.: 30 AF XY: 0.287 AC XY: 21311 AN XY: 74280

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.279

Alfa AF: 0.209 Hom.: 7563

Bravo AF: 0.306

Asia WGS AF: 0.194 AC: 674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.44

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

Other links and lift over

dbSNP: rs12329503; hg19: chr20-36007131;