7-12570874-G-T

Position:

• chr7-12570874-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001112706.3(SCIN):​c.88G>T​(p.Val30Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SCIN NM_001112706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.77

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35552144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCIN	NM_001112706.3	c.88G>T	p.Val30Leu	missense_variant	1/16	ENST00000297029.10	NP_001106177.1
SCIN	NR_156701.2	n.155G>T		non_coding_transcript_exon_variant	1/15
LOC107986768	XR_007060635.1	n.1354C>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCIN	ENST00000297029.10	c.88G>T	p.Val30Leu	missense_variant	1/16	1	NM_001112706.3	ENSP00000297029.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Mar 19, 2024

The c.88G>T (p.V30L) alteration is located in exon 1 (coding exon 1) of the SCIN gene. This alteration results from a G to T substitution at nucleotide position 88, causing the valine (V) at amino acid position 30 to be replaced by a leucine (L). 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	0.27
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	T;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.40	T
MutationAssessor	Pathogenic	3.5	M;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.25
Sift	Benign	0.050	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		0.017	B;.
Vest4		0.39
MutPred		0.59		Loss of methylation at K26 (P = 0.0726);Loss of methylation at K26 (P = 0.0726);
MVP		0.29
MPC		0.0071
ClinPred		0.96	D
GERP RS		4.9
Varity_R		0.49
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-12610500;