3-159765032-C-T

Position:

• chr3-159765032-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014575.4(SCHIP1):​c.653C>T​(p.Pro218Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000646 in 1,393,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: SCHIP1 NM_014575.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56

Genes affected

SCHIP1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2107028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCHIP1	NM_014575.4	c.653C>T	p.Pro218Leu	missense_variant	2/8	ENST00000638749.2
IQCJ-SCHIP1	NM_001197113.2	c.881C>T	p.Pro294Leu	missense_variant	5/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000646 AC: 9 AN: 1393844 Hom.: 0 Cov.: 31 AF XY: 0.00000872 AC XY: 6 AN XY: 687852

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: 0.00000835

Gnomad4 OTH exome AF: 0.00

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

Feb 17, 2022

The c.881C>T (p.P294L) alteration is located in exon 5 (coding exon 5) of the IQCJ-SCHIP1 gene. This alteration results from a C to T substitution at nucleotide position 881, causing the proline (P) at amino acid position 294 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	0.078
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.0097	.;T;.;.;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.41	N
LIST_S2	Uncertain	0.86	D;D;D;T;D
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.21	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.43	N;N;.;N;N
REVEL	Benign	0.092
Sift	Uncertain	0.0080	D;D;.;D;D
Sift4G	Benign	0.086	T;T;.;T;T
Polyphen		0.98	.;.;.;.;D
Vest4		0.13
MutPred		0.26		.;.;Loss of glycosylation at P220 (P = 0.0372);Loss of glycosylation at P220 (P = 0.0372);.;
MVP		0.043
MPC		0.91
ClinPred		0.69	D
GERP RS		4.3
Varity_R		0.17
gMVP		0.19

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

Other links and lift over

dbSNP: rs1460904314; hg19: chr3-159482821;