4-158170811-G-A

Variant names:

• chr4-158170811-G-A
• rs200249290
• NM_001128424.2:c.565C>T

Variant summary

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

The NM_001128424.2(GASK1B):​c.565C>T​(p.Arg189*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: GASK1B NM_001128424.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.673
• Publications: 1 publications found

Genes affected

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

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

ACMG classification

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

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GASK1B	NM_001128424.2	MANE Select	c.565C>T	p.Arg189*	stop_gained	Exon 2 of 5	NP_001121896.1	Q6UWH4-1
	GASK1B	NM_001031700.3		c.565C>T	p.Arg189*	stop_gained	Exon 2 of 6	NP_001026870.2	Q6UWH4-2
	GASK1B	NM_016613.7		c.565C>T	p.Arg189*	stop_gained	Exon 2 of 5	NP_057697.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GASK1B	ENST00000585682.6	TSL:1 MANE Select	c.565C>T	p.Arg189*	stop_gained	Exon 2 of 5	ENSP00000465976.1	Q6UWH4-1
	GASK1B	ENST00000393807.9	TSL:1	c.565C>T	p.Arg189*	stop_gained	Exon 2 of 6	ENSP00000377396.4	Q6UWH4-2
	GASK1B	ENST00000296530.12	TSL:1	c.565C>T	p.Arg189*	stop_gained	Exon 2 of 5	ENSP00000296530.7	Q6UWH4-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251280 AF XY: 0.00000736

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: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461858 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112004

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	32
DANN	Uncertain	1.0
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.081	N
PhyloP100		0.67
Vest4		0.13
GERP RS		2.1
PromoterAI		-0.0066	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=18/182	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs200249290; hg19: chr4-159091963; COSMIC: COSV56711371; COSMIC: COSV56711371;