3-43032445-G-A

Variant names:

• chr3-43032445-G-A
• rs1001225843
• NM_001129908.3:c.182G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001129908.3(GASK1A):​c.182G>A​(p.Arg61Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 1,551,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R61W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: GASK1A NM_001129908.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.233
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054424375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GASK1A	NM_001129908.3	c.182G>A	p.Arg61Gln	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.182G>A	p.Arg61Gln	missense_variant	Exon 2 of 5	5	NM_001129908.3	ENSP00000407301.2
ENSG00000273291	ENST00000446977.2	c.*153G>A		downstream_gene_variant		4		ENSP00000477043.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152150 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000192 AC: 3 AN: 156534 AF XY: 0.0000121

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: 0.0000496

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000250 AC: 35 AN: 1399002 Hom.: 0 Cov.: 39 AF XY: 0.0000275 AC XY: 19 AN XY: 689908

African (AFR) AF: 0.0000317 AC: 1 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35726

South Asian (SAS) AF: 0.00 AC: 0 AN: 79206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.0000269 AC: 29 AN: 1078646

Other (OTH) AF: 0.0000862 AC: 5 AN: 57992

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152150 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74332

African (AFR) AF: 0.0000483 AC: 2 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00316 AC: 1 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.0000604

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.182G>A (p.R61Q) alteration is located in exon 2 (coding exon 2) of the FAM198A gene. This alteration results from a G to A substitution at nucleotide position 182, causing the arginine (R) at amino acid position 61 to be replaced by a glutamine (Q). 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	Benign	0.069
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.7
DANN	Benign	0.96
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.23
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.034
Sift	Benign	0.44	T
Sift4G	Benign	0.46	T
Vest4		0.061
MVP		0.014
ClinPred		0.037	T
GERP RS		-3.1
gMVP		0.14
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1001225843; hg19: chr3-43073937; COSMIC: COSV107256995; COSMIC: COSV107256995;