17-38543906-C-T

Position:

• chr17-38543906-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025248.3(SRCIN1):​c.3334G>A​(p.Ala1112Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,452,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SRCIN1 NM_025248.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.564

Genes affected

SRCIN1 (HGNC:29506): (SRC kinase signaling inhibitor 1) Enables protein kinase binding activity. Involved in several processes, including regulation of dendritic spine morphogenesis; regulation of protein tyrosine kinase activity; and substrate adhesion-dependent cell spreading. Located in actin cytoskeleton and cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SRCIN1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.079999745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRCIN1	NM_025248.3	c.3334G>A	p.Ala1112Thr	missense_variant	18/19	ENST00000617146.5	NP_079524.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRCIN1	ENST00000617146.5	c.3334G>A	p.Ala1112Thr	missense_variant	18/19	1	NM_025248.3	ENSP00000484715.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1452040 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2 AN XY: 722564

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.0000225

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.3334G>A (p.A1112T) alteration is located in exon 17 (coding exon 17) of the SRCIN1 gene. This alteration results from a G to A substitution at nucleotide position 3334, causing the alanine (A) at amino acid position 1112 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.96
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.23	N
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.080	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.36	T
Sift4G	Benign	0.57	T;T
Vest4		0.21
MVP		0.068
ClinPred		0.78	D
GERP RS		0.76
Varity_R		0.026
gMVP		0.24

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: rs1348979009; hg19: chr17-36700141;