Genetic Variant SHISAL2B:p.Tyr140Cys (chr5-64717958-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001164442.2(SHISAL2B):c.419A>G(p.Tyr140Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,523,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SHISAL2B
NM_001164442.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.57

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09403327).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164442.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHISAL2B	NM_001164442.2	MANE Select	c.419A>G	p.Tyr140Cys	missense	Exon 3 of 3	NP_001157914.1	A6NKW6
	SREK1IP1	NM_173829.4	MANE Select	c.*6426T>C		downstream_gene	N/A	NP_776190.1	Q8N9Q2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SHISAL2B	ENST00000389074.6	TSL:2 MANE Select	c.419A>G	p.Tyr140Cys	missense	Exon 3 of 3	ENSP00000373726.5	A6NKW6
SHISAL2B	ENST00000506473.5	TSL:2	n.*302A>G		non_coding_transcript_exon	Exon 4 of 4	ENSP00000426145.1	D6RH14
SHISAL2B	ENST00000509189.5	TSL:2	n.*319A>G		non_coding_transcript_exon	Exon 4 of 4	ENSP00000426194.1	D6RH14

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000117

AC:

AN:

1371120

Hom.:

Cov.:

AF XY:

0.0000103

AC XY:

AN XY:

676366

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30938

American (AMR)

AF:

0.00

AC:

AN:

30886

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24930

East Asian (EAS)

AF:

0.00

AC:

AN:

35220

South Asian (SAS)

AF:

0.00

AC:

AN:

75310

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34946

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5668

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

1075876

Other (OTH)

AF:

0.00

AC:

AN:

57346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0029

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.53

M_CAP

Benign

0.0076

MetaRNN

Benign

0.094

MetaSVM

Benign

-1.1

PhyloP100

1.6

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.16

REVEL

Benign

0.050

Sift

Benign

0.16

Sift4G

Benign

0.17

Vest4

0.33

MutPred

0.35

Loss of helix (P = 0.0558)

MVP

0.099

MPC

0.13

ClinPred

0.11

GERP RS

0.52

Varity_R

0.053

gMVP

0.20

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over