3-43032279-C-T

Variant names:

• chr3-43032279-C-T
• rs557007733
• NM_001129908.3:c.16C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001129908.3(GASK1A):​c.16C>T​(p.Arg6Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000146 in 1,370,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). 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)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: GASK1A NM_001129908.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00900
• 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=0.09280765).
• BP6: Variant 3-43032279-C-T is Benign according to our data. Variant chr3-43032279-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3098705.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.16C>T	p.Arg6Trp	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.16C>T	p.Arg6Trp	missense_variant	Exon 2 of 5	5	NM_001129908.3	ENSP00000407301.2
ENSG00000273291	ENST00000446977.2	c.290C>T	p.Pro97Leu	missense_variant	Exon 5 of 5	4		ENSP00000477043.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000135 AC: 2 AN: 147916 AF XY: 0.0000128

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000424

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000146 AC: 20 AN: 1370558 Hom.: 0 Cov.: 38 AF XY: 0.0000194 AC XY: 13 AN XY: 670096

African (AFR) AF: 0.00 AC: 0 AN: 30898

American (AMR) AF: 0.0000583 AC: 2 AN: 34288

Ashkenazi Jewish (ASJ) AF: 0.0000412 AC: 1 AN: 24260

East Asian (EAS) AF: 0.00 AC: 0 AN: 35030

South Asian (SAS) AF: 0.0000260 AC: 2 AN: 76994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5586

European-Non Finnish (NFE) AF: 0.0000132 AC: 14 AN: 1058000

Other (OTH) AF: 0.0000177 AC: 1 AN: 56638

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

ExAC AF: 0.0000395 AC: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 27, 2024

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	0.044
BayesDel_addAF	Benign	0.0014	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.2
DANN	Benign	0.80
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.093	T
PhyloP100		-0.0090
Sift4G	Benign	0.25	T
MVP		0.27
ClinPred		0.13	T
GERP RS		1.1
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs557007733; hg19: chr3-43073771;