Genetic Variant SCIN:c.981+264G>C (chr7-12626114-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001112706.3(SCIN):c.981+264G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000398 in 251,536 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000040 ( 0 hom. )

Consequence

SCIN
NM_001112706.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.451

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SCIN	NM_001112706.3 link	c.981+264G>C	intron_variant	Intron 7 of 15	ENST00000297029.10	NP_001106177.1	Q9Y6U3-1
SCIN	NM_033128.3 link	c.240+264G>C	intron_variant	Intron 5 of 13		NP_149119.1	Q9Y6U3-3
SCIN	NR_156701.2 link	n.1048+264G>C	intron_variant	Intron 7 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCIN	ENST00000297029.10 link	c.981+264G>C		intron_variant	Intron 7 of 15	1	NM_001112706.3	ENSP00000297029.5		Q9Y6U3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000398

AC:

AN:

251536

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

129928

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

6736

American (AMR)

AF:

0.00

AC:

AN:

8710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8574

East Asian (EAS)

AF:

0.00

AC:

AN:

18126

South Asian (SAS)

AF:

0.00

AC:

AN:

15994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16638

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1180

European-Non Finnish (NFE)

AF:

0.00000626

AC:

AN:

159768

Other (OTH)

AF:

0.00

AC:

AN:

15810

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.52

(source)

DANN

Benign

0.65

PhyloP100

-0.45

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over