chr4-158171314-G-T

Variant names:

• chr4-158171314-G-T
• rs1223992577
• NM_001128424.2:c.62C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001128424.2(GASK1B):​c.62C>A​(p.Pro21Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P21L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GASK1B NM_001128424.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00
• Publications: 2 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20407432).

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.62C>A	p.Pro21Gln	missense	Exon 2 of 5	NP_001121896.1	Q6UWH4-1
	GASK1B	NM_001031700.3		c.62C>A	p.Pro21Gln	missense	Exon 2 of 6	NP_001026870.2	Q6UWH4-2
	GASK1B	NM_016613.7		c.62C>A	p.Pro21Gln	missense	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.62C>A	p.Pro21Gln	missense	Exon 2 of 5	ENSP00000465976.1	Q6UWH4-1
	GASK1B	ENST00000393807.9	TSL:1	c.62C>A	p.Pro21Gln	missense	Exon 2 of 6	ENSP00000377396.4	Q6UWH4-2
	GASK1B	ENST00000296530.12	TSL:1	c.62C>A	p.Pro21Gln	missense	Exon 2 of 5	ENSP00000296530.7	Q6UWH4-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Benign	0.97
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.0
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.046
Sift	Benign	0.045	D
Sift4G	Benign	0.13	T
Vest4		0.30
MutPred		0.51		Gain of helix (P = 0.0117)
MVP		0.31
MPC		0.60
ClinPred		0.90	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
gMVP		0.51
Mutation Taster		=92/8	polymorphism

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: rs1223992577; hg19: chr4-159092466;