Genetic Variant SHISAL2B:p.Ala131Thr (chr5-64717930-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001164442.2(SHISAL2B):c.391G>A(p.Ala131Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000263 in 1,520,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

SHISAL2B
NM_001164442.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.784

Variant links:

Genes affected

SHISAL2B (HGNC:34236): (shisa like 2B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SHISAL2B links:

SREK1IP1 (HGNC:26716): (SREK1 interacting protein 1) Predicted to enable nucleic acid binding activity and zinc ion binding activity. Predicted to be involved in RNA splicing and mRNA processing. [provided by Alliance of Genome Resources, Apr 2022]

SREK1IP1 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=0.081893235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHISAL2B	NM_001164442.2 link	c.391G>A	p.Ala131Thr	missense_variant	Exon 3 of 3	ENST00000389074.6	NP_001157914.1	A6NKW6
SREK1IP1	NM_173829.4 link	c.*6454C>T		downstream_gene_variant		ENST00000513458.9	NP_776190.1	Q8N9Q2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHISAL2B	ENST00000389074.6 link	c.391G>A	p.Ala131Thr	missense_variant	Exon 3 of 3	2	NM_001164442.2	ENSP00000373726.5		A6NKW6
SREK1IP1	ENST00000513458.9 link	c.*6454C>T		downstream_gene_variant		1	NM_173829.4	ENSP00000427401.3		Q8N9Q2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000219

AC:

AN:

1368586

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

675048

show subpopulations

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:

0.00000279

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152064

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 10, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.391G>A (p.A131T) alteration is located in exon 3 (coding exon 3) of the FAM159B gene. This alteration results from a G to A substitution at nucleotide position 391, causing the alanine (A) at amino acid position 131 to be replaced by a threonine (T). 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

0.067

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0033

Eigen

Benign

-0.056

Eigen_PC

Benign

-0.025

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.52

M_CAP

Benign

0.0057

MetaRNN

Benign

0.082

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.47

REVEL

Benign

0.034

Sift

Benign

0.31

Sift4G

Benign

0.067

Vest4

0.040

MutPred

0.16

Gain of relative solvent accessibility (P = 0.0082);

MVP

0.076

MPC

0.097

ClinPred

0.79

GERP RS

1.9

Varity_R

0.036

gMVP

0.14

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