3-159764810-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.431C>T(p.Pro144Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000455 in 1,428,412 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P144S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: SCHIP1 NM_014575.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.680

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=0.18945068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCHIP1	NM_014575.4	c.431C>T	p.Pro144Leu	missense_variant	2/8	ENST00000638749.2
IQCJ-SCHIP1	NM_001197113.2	c.659C>T	p.Pro220Leu	missense_variant	5/11

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000269 AC: 5 AN: 185988 Hom.: 0 AF XY: 0.0000195 AC XY: 2 AN XY: 102488

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000330

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000522

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000455 AC: 65 AN: 1428412 Hom.: 0 Cov.: 31 AF XY: 0.0000339 AC XY: 24 AN XY: 707840

Gnomad4 AFR exome AF: 0.0000310

Gnomad4 AMR exome AF: 0.0000242

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000122

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000501

Gnomad4 OTH exome AF: 0.000119

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000678 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000260 AC: 3

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

Jun 29, 2023

The c.659C>T (p.P220L) 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 659, causing the proline (P) at amino acid position 220 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	0.083
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	18
Dann	Uncertain	1.0
Eigen	Benign	0.070
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.71	T;T;T;T;T;T;T
M_CAP	Pathogenic	0.57	D
MetaRNN	Benign	0.19	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.5	N;N;.;N;.;N;.
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D;D;.;D;.;D;.
Sift4G	Uncertain	0.0090	D;D;.;T;.;T;.
Polyphen		0.80	.;.;.;.;.;P;.
Vest4		0.22
MutPred		0.13		.;.;Loss of glycosylation at P145 (P = 0.017);Loss of glycosylation at P145 (P = 0.017);.;.;.;
MVP		0.14
MPC		0.32
ClinPred		0.18	T
GERP RS		4.8
Varity_R		0.19
gMVP		0.42

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: rs201276102; hg19: chr3-159482599;