Variant rs361863 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.82A>C(p.Ser28Arg) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S28G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Consequence

ISX
NM_001303508.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.478

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:

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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=0.07810038).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ISX	NM_001303508.2 linkuse as main transcript	c.82A>C	p.Ser28Arg	missense_variant	2/5	ENST00000404699.7
ISX	XM_047441598.1 linkuse as main transcript	c.82A>C	p.Ser28Arg	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ISX	ENST00000404699.7 linkuse as main transcript	c.82A>C	p.Ser28Arg	missense_variant	2/5	1	NM_001303508.2	P1
ISX	ENST00000308700.6 linkuse as main transcript	c.82A>C	p.Ser28Arg	missense_variant	1/4	1		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

T;T

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.14

.;T

M_CAP

Benign

0.066

MetaRNN

Benign

0.078

T;T

MetaSVM

Benign

-0.33

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.20

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.013

D;D

Polyphen

0.0

B;B

Vest4

0.066

MutPred

0.23

Gain of MoRF binding (P = 0.0161);Gain of MoRF binding (P = 0.0161);

MVP

0.82

MPC

0.010

ClinPred

0.65

GERP RS

5.1

Varity_R

0.17

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over