4-158130843-C-A

Variant names:

• chr4-158130843-C-A
• NM_001128424.2:c.1295G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000585682.6(GASK1B):​c.1295G>T​(p.Gly432Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GASK1B ENST00000585682.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.59
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GASK1B	NM_001128424.2	c.1295G>T	p.Gly432Val	missense_variant	Exon 4 of 5	ENST00000585682.6	NP_001121896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GASK1B	ENST00000585682.6	c.1295G>T	p.Gly432Val	missense_variant	Exon 4 of 5	1	NM_001128424.2	ENSP00000465976.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1319G>T (p.G440V) alteration is located in exon 5 (coding exon 4) of the FAM198B gene. This alteration results from a G to T substitution at nucleotide position 1319, causing the glycine (G) at amino acid position 440 to be replaced by a valine (V). 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	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	23
DANN	Uncertain	1.0
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	.;D;D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.74	D;D;D;D;D
MetaSVM	Benign	-0.43	T
PhyloP100		3.6
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-7.8	.;D;D;.;.
REVEL	Uncertain	0.45
Sift	Uncertain	0.0020	.;D;D;.;.
Sift4G	Uncertain	0.0040	D;D;D;.;D
Vest4		0.74
MutPred		0.54		Gain of methylation at K431 (P = 0.0446);Gain of methylation at K431 (P = 0.0446);.;.;.;
MVP		0.49
MPC		0.74
ClinPred		0.97	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.90
Mutation Taster		=39/61	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr4-159051995;