Variant 22-44285554-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_001099294.2(SHISAL1):c.473C>T(p.Pro158Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000611 in 1,538,262 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: 𝑓 0.000068 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

SHISAL1
NM_001099294.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.33

Variant links:

Genes affected

SHISAL1 (HGNC:29335): (shisa like 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SHISAL1 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=0.1883755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHISAL1	NM_001099294.2 linkuse as main transcript	c.473C>T	p.Pro158Leu	missense_variant	4/5	ENST00000381176.5	NP_001092764.1
SHISAL1	XM_005261790.4 linkuse as main transcript	c.473C>T	p.Pro158Leu	missense_variant	4/5		XP_005261847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHISAL1	ENST00000381176.5 linkuse as main transcript	c.473C>T	p.Pro158Leu	missense_variant	4/5	5	NM_001099294.2	ENSP00000370568	P1

Frequencies

GnomAD3 genomes

AF:

0.0000680

AC:

AN:

147058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000338

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000309

Gnomad OTH

AF:

0.000488

GnomAD3 exomes

AF:

0.0000938

AC:

AN:

245272

Hom.:

AF XY:

0.0000675

AC XY:

AN XY:

133412

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000436

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000562

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000273

Gnomad OTH exome

AF:

0.000500

GnomAD4 exome

AF:

0.0000604

AC:

AN:

1391204

Hom.:

Cov.:

AF XY:

0.0000635

AC XY:

AN XY:

692880

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.000455

Gnomad4 ASJ exome

AF:

0.0000784

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000314

Gnomad4 OTH exome

AF:

0.000226

GnomAD4 genome

AF:

0.0000680

AC:

AN:

147058

Hom.:

Cov.:

AF XY:

0.0000696

AC XY:

AN XY:

71826

show subpopulations

Gnomad4 AFR

AF:

0.0000244

Gnomad4 AMR

AF:

0.000338

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000309

Gnomad4 OTH

AF:

0.000488

Alfa

AF:

0.000141

Hom.:

Bravo

AF:

0.000227

ExAC

AF:

0.0000940

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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

Apr 04, 2023

The c.473C>T (p.P158L) alteration is located in exon 4 (coding exon 3) of the KIAA1644 gene. This alteration results from a C to T substitution at nucleotide position 473, causing the proline (P) at amino acid position 158 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

0.091

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Benign

0.057

Eigen_PC

Benign

0.013

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.68

M_CAP

Benign

0.019

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.88

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.13

Sift

Uncertain

0.010

Sift4G

Uncertain

0.041

Polyphen

0.98

Vest4

0.18

MutPred

0.37

Loss of relative solvent accessibility (P = 0.008);

MVP

0.12

MPC

0.36

ClinPred

0.13

GERP RS

4.0

Varity_R

0.12

gMVP

0.26

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

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