3-43032530-G-T

Variant names:

• chr3-43032530-G-T
• rs770256828
• NM_001129908.3:c.267G>T

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.267G>T​(p.Leu89Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,397,294 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: GASK1A NM_001129908.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655
• 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=0.07221809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GASK1A	NM_001129908.3	c.267G>T	p.Leu89Phe	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.267G>T	p.Leu89Phe	missense_variant	Exon 2 of 5	5	NM_001129908.3	ENSP00000407301.2
ENSG00000273291	ENST00000446977.2	c.*238G>T		downstream_gene_variant		4		ENSP00000477043.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000128 AC: 2 AN: 156362 AF XY: 0.00

Gnomad AFR exome AF: 0.000125

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1397294 Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0 AN XY: 688602

African (AFR) AF: 0.00 AC: 0 AN: 31562

American (AMR) AF: 0.00 AC: 0 AN: 35656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25172

East Asian (EAS) AF: 0.00 AC: 0 AN: 35642

South Asian (SAS) AF: 0.00 AC: 0 AN: 79202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077200

Other (OTH) AF: 0.0000173 AC: 1 AN: 57904

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.0
DANN	Uncertain	1.0
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.66
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.032
Sift	Benign	0.039	D
Sift4G	Benign	0.13	T
Vest4		0.10
MutPred		0.27		Gain of glycosylation at S87 (P = 0.0325);
MVP		0.030
ClinPred		0.46	T
GERP RS		-1.1
gMVP		0.11
Mutation Taster		=95/5	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: rs770256828; hg19: chr3-43074022;