3-43032381-G-A

Variant names:

• chr3-43032381-G-A
• rs571794011
• NM_001129908.3:c.118G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001129908.3(GASK1A):​c.118G>A​(p.Ala40Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000735 in 1,551,566 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000041 (0 hom.)
• Consequence: GASK1A NM_001129908.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.24
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014774829).
• BP6: Variant 3-43032381-G-A is Benign according to our data. Variant chr3-43032381-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3098695.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GASK1A	NM_001129908.3	c.118G>A	p.Ala40Thr	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.118G>A	p.Ala40Thr	missense_variant	Exon 2 of 5	5	NM_001129908.3	ENSP00000407301.2
ENSG00000273291	ENST00000446977.2	c.*89G>A		downstream_gene_variant		4		ENSP00000477043.1

Frequencies

GnomAD3 genomes AF: 0.000368 AC: 56 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000958 AC: 15 AN: 156506 AF XY: 0.0000482

Gnomad AFR exome AF: 0.00138

Gnomad AMR exome AF: 0.0000811

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000330

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000414 AC: 58 AN: 1399284 Hom.: 0 Cov.: 39 AF XY: 0.0000420 AC XY: 29 AN XY: 690142

African (AFR) AF: 0.000506 AC: 16 AN: 31598

American (AMR) AF: 0.000112 AC: 4 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35732

South Asian (SAS) AF: 0.0000505 AC: 4 AN: 79214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.0000260 AC: 28 AN: 1078890

Other (OTH) AF: 0.0000862 AC: 5 AN: 58004

GnomAD4 genome AF: 0.000368 AC: 56 AN: 152282 Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27 AN XY: 74452

African (AFR) AF: 0.00120 AC: 50 AN: 41562

American (AMR) AF: 0.0000654 AC: 1 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000320 Hom.: 0

Bravo AF: 0.000389

ExAC AF: 0.0000364 AC: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 03, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.12
DANN	Benign	0.57
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.98	T
PhyloP100		-1.2
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.028
Sift	Benign	0.78	T
Sift4G	Benign	0.47	T
Vest4		0.043
MVP		0.014
ClinPred		0.0058	T
GERP RS		-3.7
gMVP		0.11
Mutation Taster		=88/12	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: rs571794011; hg19: chr3-43073873; COSMIC: COSV99826385; COSMIC: COSV99826385;