chr3-159764479-G-T

Position:

• chr3-159764479-G-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.100G>T​(p.Ala34Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000278 in 1,438,902 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: 0.0000028 (0 hom.)
• Consequence: SCHIP1 NM_014575.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.23

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=0.13169777).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCHIP1	NM_014575.4	c.100G>T	p.Ala34Ser	missense_variant	2/8	ENST00000638749.2
IQCJ-SCHIP1	NM_001197113.2	c.328G>T	p.Ala110Ser	missense_variant	5/11

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000965 AC: 2 AN: 207316 Hom.: 0 AF XY: 0.00000899 AC XY: 1 AN XY: 111244

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000130

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: 0.00000278 AC: 4 AN: 1438902 Hom.: 0 Cov.: 31 AF XY: 0.00000421 AC XY: 3 AN XY: 713242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000103

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

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 24, 2022

The c.328G>T (p.A110S) alteration is located in exon 5 (coding exon 5) of the IQCJ-SCHIP1 gene. This alteration results from a G to T substitution at nucleotide position 328, causing the alanine (A) at amino acid position 110 to be replaced by a serine (S). 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	0.087
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	.;T;.;.;.;.;.;.;.;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.029
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.78	T;T;T;T;T;T;T;T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.13	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	0.52	D;D;D;D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.33	N;N;.;.;.;.;N;.;N;.
REVEL	Benign	0.042
Sift	Benign	0.10	T;D;.;.;.;.;D;.;T;.
Sift4G	Benign	1.0	T;T;.;.;.;.;T;.;T;.
Polyphen		0.050	.;.;.;.;.;.;.;.;B;.
Vest4		0.44
MutPred		0.19		.;.;.;.;.;Gain of glycosylation at S37 (P = 0.0044);Gain of glycosylation at S37 (P = 0.0044);.;.;.;
MVP		0.14
MPC		0.98
ClinPred		0.48	T
GERP RS		3.6
Varity_R		0.15
gMVP		0.15

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: rs1468853366; hg19: chr3-159482268;