Genetic Variant NM_001128424.2:c.524T>C (chr4-158170852-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001128424.2(GASK1B):c.524T>C(p.Ile175Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I175F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

GASK1B
NM_001128424.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.02

Publications

0 publications found

Variant links:

Genes affected

GASK1B (HGNC:25312): (golgi associated kinase 1B) Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

GASK1B links:

GASK1B-AS1 (HGNC:53132): (GASK1B antisense RNA 1)

GASK1B-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03621).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128424.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GASK1B	NM_001128424.2	MANE Select	c.524T>C	p.Ile175Thr	missense	Exon 2 of 5	NP_001121896.1	Q6UWH4-1
GASK1B	NM_001031700.3		c.524T>C	p.Ile175Thr	missense	Exon 2 of 6	NP_001026870.2	Q6UWH4-2
GASK1B	NM_016613.7		c.524T>C	p.Ile175Thr	missense	Exon 2 of 5	NP_057697.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GASK1B	ENST00000585682.6	TSL:1 MANE Select	c.524T>C	p.Ile175Thr	missense	Exon 2 of 5	ENSP00000465976.1	Q6UWH4-1
GASK1B	ENST00000393807.9	TSL:1	c.524T>C	p.Ile175Thr	missense	Exon 2 of 6	ENSP00000377396.4	Q6UWH4-2
GASK1B	ENST00000296530.12	TSL:1	c.524T>C	p.Ile175Thr	missense	Exon 2 of 5	ENSP00000296530.7	Q6UWH4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251404

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

0.052

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.9

(source)

DANN

Benign

0.52

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.48

M_CAP

Benign

0.0062

MetaRNN

Benign

0.036

MetaSVM

Benign

-1.0

PhyloP100

-1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

0.46

REVEL

Benign

0.0090

Sift

Benign

0.14

Sift4G

Benign

0.80

Vest4

0.047

MutPred

0.40

Loss of stability (P = 0.0023)

MVP

0.030

MPC

0.19

ClinPred

0.032

GERP RS

-1.5

PromoterAI

-0.019

Neutral

(source)

gMVP

0.21

Mutation Taster

=92/8

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over