17-38533413-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_025248.3(SRCIN1):ā€‹c.3436G>Cā€‹(p.Glu1146Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 27)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

SRCIN1
NM_025248.3 missense

Scores

5
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.97
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.14626807).
BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SRCIN1NM_025248.3 linkuse as main transcriptc.3436G>C p.Glu1146Gln missense_variant 19/19 ENST00000617146.5 NP_079524.2 Q9C0H9-5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SRCIN1ENST00000617146.5 linkuse as main transcriptc.3436G>C p.Glu1146Gln missense_variant 19/191 NM_025248.3 ENSP00000484715.1 Q9C0H9-5
SRCIN1ENST00000621492.4 linkuse as main transcriptc.3538G>C p.Glu1180Gln missense_variant 20/205 ENSP00000483931.1 A0A087X165

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152020
Hom.:
0
Cov.:
27
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1461138
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
726792
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152020
Hom.:
0
Cov.:
27
AF XY:
0.00
AC XY:
0
AN XY:
74240
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000244
AC:
2
ExAC
AF:
0.0000166
AC:
2

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 submitterclinical testingAmbry GeneticsNov 08, 2022The c.3436G>C (p.E1146Q) alteration is located in exon 18 (coding exon 18) of the SRCIN1 gene. This alteration results from a G to C substitution at nucleotide position 3436, causing the glutamic acid (E) at amino acid position 1146 to be replaced by a glutamine (Q). 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
0.34
BayesDel_addAF
Benign
-0.096
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
24
DANN
Uncertain
1.0
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.92
D
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-0.95
T
PrimateAI
Uncertain
0.72
T
Sift4G
Benign
0.12
T;T
Vest4
0.14
MVP
0.082
ClinPred
0.75
D
GERP RS
5.3
Varity_R
0.13
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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: rs374609814; hg19: chr17-36689648; API