3-159764666-A-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.287A>T(p.Glu96Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SCHIP1 NM_014575.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.97

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=0.12841845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCHIP1	NM_014575.4	c.287A>T	p.Glu96Val	missense_variant	2/8	ENST00000638749.2
IQCJ-SCHIP1	NM_001197113.2	c.515A>T	p.Glu172Val	missense_variant	5/11

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000466 AC: 1 AN: 214726 Hom.: 0 AF XY: 0.00000866 AC XY: 1 AN XY: 115514

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000622

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440668 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 714238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000258

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000825 AC: 1

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

Dec 04, 2023

The c.515A>T (p.E172V) alteration is located in exon 5 (coding exon 5) of the IQCJ-SCHIP1 gene. This alteration results from a A to T substitution at nucleotide position 515, causing the glutamic acid (E) at amino acid position 172 to be replaced by a valine (V). 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	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	20
Dann	Uncertain	0.98
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.65	T;T;T;T;T;T;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.13	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.74	D;D;D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.79	N;N;.;.;N;.;N;.
REVEL	Benign	0.081
Sift	Benign	0.036	D;D;.;.;D;.;T;.
Sift4G	Uncertain	0.056	T;D;.;.;D;.;D;.
Polyphen		0.46	.;.;.;.;.;.;P;.
Vest4		0.29
MutPred		0.14		.;.;.;Loss of solvent accessibility (P = 0.0174);Loss of solvent accessibility (P = 0.0174);.;.;.;
MVP		0.043
MPC		1.1
ClinPred		0.26	T
GERP RS		1.6
Varity_R		0.10
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs754682151; hg19: chr3-159482455;