Variant chr22-35082530-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001303508.2(ISX):c.242G>A(p.Ser81Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ISX
NM_001303508.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.34

Variant links:

Genes affected

ISX (HGNC:28084): (intestine specific homeobox) Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This gene is a member of the RAXLX homeobox gene family. [provided by RefSeq, Jul 2008]

ISX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.12880698).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ISX	NM_001303508.2 linkuse as main transcript	c.242G>A	p.Ser81Asn	missense_variant	3/5	ENST00000404699.7	NP_001290437.1	Q2M1V0
ISX	XM_047441598.1 linkuse as main transcript	c.242G>A	p.Ser81Asn	missense_variant	2/4		XP_047297554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ISX	ENST00000404699.7 linkuse as main transcript	c.242G>A	p.Ser81Asn	missense_variant	3/5	1	NM_001303508.2	ENSP00000386037.1		Q2M1V0
ISX	ENST00000308700.6 linkuse as main transcript	c.242G>A	p.Ser81Asn	missense_variant	2/4	1		ENSP00000311492.6		Q2M1V0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461726

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727174

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2024

The c.242G>A (p.S81N) alteration is located in exon 2 (coding exon 2) of the ISX gene. This alteration results from a G to A substitution at nucleotide position 242, causing the serine (S) at amino acid position 81 to be replaced by an asparagine (N). 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

0.095

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.046

T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.12

.;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.13

T;T

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

1.5

L;L

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.51

N;N

REVEL

Benign

0.18

Sift

Benign

0.46

T;T

Sift4G

Benign

0.98

T;T

Polyphen

0.013

B;B

Vest4

0.082

MutPred

0.38

Loss of phosphorylation at S81 (P = 0.0029);Loss of phosphorylation at S81 (P = 0.0029);

MVP

0.88

MPC

0.010

ClinPred

0.11

GERP RS

2.8

Varity_R

0.059

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over