3-159866205-C-T

Position:

• chr3-159866205-C-T

Variant summary

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

The NM_014575.4(SCHIP1):​c.802C>T​(p.Leu268Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCHIP1 NM_014575.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.68

Genes affected

SCHIP1 (HGNC:15678): (schwannomin interacting protein 1) Enables identical protein binding activity. Predicted to be involved in positive regulation of hippo signaling. Predicted to act upstream of or within several processes, including animal organ development; face morphogenesis; and fibroblast migration. Located in several cellular components, including cell junction; cytosol; and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

IQCJ-SCHIP1 (HGNC:):

ACMG classification

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	UniProt
SCHIP1	NM_014575.4	c.802C>T	p.Leu268Phe	missense_variant	3/8	ENST00000638749.2
IQCJ-SCHIP1	NM_001197113.2	c.1030C>T	p.Leu344Phe	missense_variant	6/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCHIP1	ENST00000445224.6	c.73C>T	p.Leu25Phe	missense_variant	2/7	1		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Nov 07, 2022

The c.1030C>T (p.L344F) alteration is located in exon 6 (coding exon 6) of the IQCJ-SCHIP1 gene. This alteration results from a C to T substitution at nucleotide position 1030, causing the leucine (L) at amino acid position 344 to be replaced by a phenylalanine (F). 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	0.91
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.030	.;T;.;.;.;.;.;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;D;D;D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.51	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.43	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.4	N;N;.;N;N;N;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.013	D;D;.;D;T;T;T;T
Sift4G	Uncertain	0.039	D;D;.;D;D;D;D;D
Polyphen		1.0, 0.0030	.;.;.;.;.;D;.;B
Vest4		0.47
MutPred		0.69		.;.;Gain of methylation at K265 (P = 0.0655);.;.;.;.;.;
MVP		0.33
MPC		1.1, 1.3
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.53
gMVP		0.59

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: chr3-159583994;