Variant 7-12604525-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_033128.3(SCIN):c.-214G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,551,474 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

SCIN
NM_033128.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.734

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 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	Protein	UniProt
SCIN	NM_001112706.3 linkuse as main transcript	c.528G>C	p.Gln176His	missense_variant	4/16	ENST00000297029.10	NP_001106177.1	Q9Y6U3-1
SCIN	NM_033128.3 linkuse as main transcript	c.-214G>C		5_prime_UTR_premature_start_codon_gain_variant	2/14		NP_149119.1	Q9Y6U3-3
SCIN	NM_033128.3 linkuse as main transcript	c.-214G>C		5_prime_UTR_variant	2/14		NP_149119.1	Q9Y6U3-3
SCIN	NR_156701.2 linkuse as main transcript	n.595G>C		non_coding_transcript_exon_variant	4/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCIN	ENST00000297029.10 linkuse as main transcript	c.528G>C	p.Gln176His	missense_variant	4/16	1	NM_001112706.3	ENSP00000297029.5		Q9Y6U3-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152072

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000127

AC:

AN:

156986

Hom.:

AF XY:

0.0000120

AC XY:

AN XY:

83102

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000329

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000522

AC:

AN:

1399402

Hom.:

Cov.:

AF XY:

0.0000449

AC XY:

AN XY:

690206

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:

0.0000649

Gnomad4 OTH exome

AF:

0.0000517

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152072

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74276

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

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

Jul 12, 2023

The c.528G>C (p.Q176H) alteration is located in exon 4 (coding exon 4) of the SCIN gene. This alteration results from a G to C substitution at nucleotide position 528, causing the glutamine (Q) at amino acid position 176 to be replaced by a histidine (H). 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

Pathogenic

0.57

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Pathogenic

0.14

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.087

T;.;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.053

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.044

MetaRNN

Uncertain

0.57

D;D;D

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.9

M;.;.

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-4.2

D;D;D

REVEL

Uncertain

0.33

Sift

Benign

0.030

D;D;D

Sift4G

Benign

0.063

T;D;D

Polyphen

0.020

B;.;.

Vest4

0.74

MutPred

0.66

Gain of loop (P = 0.2045);.;.;

MVP

0.42

MPC

0.030

ClinPred

0.80

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.84

gMVP

0.75

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