Variant 7-12581112-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001112706.3(SCIN):c.407C>T(p.Ala136Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000902 in 1,551,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000093 ( 0 hom. )

Consequence

SCIN
NM_001112706.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.64

Variant links:

Genes affected

SCIN (HGNC:21695): (scinderin) SCIN is a Ca(2+)-dependent actin-severing and -capping protein (Zunino et al., 2001 [PubMed 11568009]).[supplied by OMIM, May 2010]

SCIN links:

SCIN (HGNC:):

SCIN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05801058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCIN	NM_001112706.3 linkuse as main transcript	c.407C>T	p.Ala136Val	missense_variant	3/16	ENST00000297029.10	NP_001106177.1	Q9Y6U3-1
SCIN	NR_156701.2 linkuse as main transcript	n.474C>T		non_coding_transcript_exon_variant	3/15
LOC107986768	XR_007060635.1 linkuse as main transcript	n.846+7394G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SCIN	ENST00000297029.10 linkuse as main transcript	c.407C>T	p.Ala136Val	missense_variant	3/16	1	NM_001112706.3	ENSP00000297029.5	Q9Y6U3-1
SCIN	ENST00000341757.9 linkuse as main transcript	n.407C>T		non_coding_transcript_exon_variant	3/15	1		ENSP00000341375.5	Q9Y6U3-2
SCIN	ENST00000417018.1 linkuse as main transcript	c.*7C>T		downstream_gene_variant		4		ENSP00000404380.1	C9JGB6

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152172

Hom.:

Cov.:

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000383

AC:

AN:

156574

Hom.:

AF XY:

0.0000482

AC XY:

AN XY:

82978

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000551

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000929

AC:

AN:

1399138

Hom.:

Cov.:

AF XY:

0.00000869

AC XY:

AN XY:

690078

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000336

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

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

Dec 15, 2023

The c.407C>T (p.A136V) alteration is located in exon 3 (coding exon 3) of the SCIN gene. This alteration results from a C to T substitution at nucleotide position 407, causing the alanine (A) at amino acid position 136 to be replaced by a valine (V). 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

0.15

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0050

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.84

M_CAP

Benign

0.023

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.32

PrimateAI

Uncertain

0.54

PROVEAN

Benign

1.2

REVEL

Benign

0.067

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.058

Vest4

0.12

MutPred

0.35

Gain of MoRF binding (P = 0.1045);

MVP

0.47

MPC

0.013

ClinPred

0.085

GERP RS

4.3

Varity_R

0.21

gMVP

0.36

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over