3-43032280-G-C

Variant names:

• chr3-43032280-G-C
• rs368973802
• NM_001129908.3:c.17G>C

Variant summary

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

The NM_001129908.3(GASK1A):​c.17G>C​(p.Arg6Pro) 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. 14/20 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. R6Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GASK1A NM_001129908.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.05
• Publications: 0 publications found

Genes affected

GASK1A (HGNC:24485): (golgi associated kinase 1A) Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000273291 (HGNC:):

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=0.19785395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GASK1A	NM_001129908.3	c.17G>C	p.Arg6Pro	missense_variant	Exon 2 of 5	ENST00000430121.3	NP_001123380.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GASK1A	ENST00000430121.3	c.17G>C	p.Arg6Pro	missense_variant	Exon 2 of 5	5	NM_001129908.3	ENSP00000407301.2
ENSG00000273291	ENST00000446977.2	c.291G>C	p.Pro97Pro	synonymous_variant	Exon 5 of 5	4		ENSP00000477043.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Uncertain	0.99
Eigen	Benign	-0.12
Eigen_PC	Benign	0.0093
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.0
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.053
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.018	D
Vest4		0.23
MutPred		0.52		Loss of helix (P = 0.0068);
MVP		0.22
ClinPred		0.73	D
GERP RS		4.8
gMVP		0.24
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs368973802; hg19: chr3-43073772;