3-43032343-C-T

Variant names:

• chr3-43032343-C-T
• rs138304813
• NM_001129908.3:c.80C>T

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.80C>T​(p.Ala27Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,551,362 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A27T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00074 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000081 (0 hom.)
• Consequence: GASK1A NM_001129908.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.473
• Publications: 1 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=0.00404799).
• BP6: Variant 3-43032343-C-T is Benign according to our data. Variant chr3-43032343-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3098715.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.80C>T	p.Ala27Val	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.80C>T	p.Ala27Val	missense_variant	Exon 2 of 5	5	NM_001129908.3	ENSP00000407301.2
ENSG00000273291	ENST00000446977.2	c.*51C>T		downstream_gene_variant		4		ENSP00000477043.1

Frequencies

GnomAD3 genomes AF: 0.000729 AC: 111 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000141 AC: 22 AN: 156356 AF XY: 0.000169

Gnomad AFR exome AF: 0.00202

Gnomad AMR exome AF: 0.0000812

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: 0.0000808 AC: 113 AN: 1399034 Hom.: 0 Cov.: 39 AF XY: 0.0000797 AC XY: 55 AN XY: 689968

African (AFR) AF: 0.00234 AC: 74 AN: 31596

American (AMR) AF: 0.0000841 AC: 3 AN: 35668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25174

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.0000505 AC: 4 AN: 79162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49284

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5698

European-Non Finnish (NFE) AF: 0.0000176 AC: 19 AN: 1078722

Other (OTH) AF: 0.000207 AC: 12 AN: 57996

GnomAD4 genome AF: 0.000735 AC: 112 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.000779 AC XY: 58 AN XY: 74474

African (AFR) AF: 0.00243 AC: 101 AN: 41572

American (AMR) AF: 0.000392 AC: 6 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000709 Hom.: 0

Bravo AF: 0.000729

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00217 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000222 AC: 6

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 17, 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	0.082
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.14
DANN	Benign	0.85
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.47
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.28	N
REVEL	Benign	0.013
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.044
MVP		0.030
ClinPred		0.0027	T
GERP RS		-5.8
gMVP		0.13
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs138304813; hg19: chr3-43073835; COSMIC: COSV56181566; COSMIC: COSV56181566;