NM_001129908.3:c.616G>C

Variant names:

• chr3-43032879-G-C
• rs115672213
• NM_001129908.3:c.616G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001129908.3(GASK1A):​c.616G>C​(p.Ala206Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000847 in 1,550,448 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (12 hom., cov: 33)
  • Exomes 𝑓: 0.00043 (2 hom.)
• Consequence: GASK1A NM_001129908.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.160
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004083216).
• BP6: Variant 3-43032879-G-C is Benign according to our data. Variant chr3-43032879-G-C is described in ClinVar as [Benign]. Clinvar id is 789982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00464 (707/152280) while in subpopulation AFR AF = 0.0164 (682/41564). AF 95% confidence interval is 0.0154. There are 12 homozygotes in GnomAd4. There are 331 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GASK1A	NM_001129908.3	c.616G>C	p.Ala206Pro	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.616G>C	p.Ala206Pro	missense_variant	Exon 2 of 5	5	NM_001129908.3	ENSP00000407301.2

Frequencies

GnomAD3 genomes AF: 0.00459 AC: 699 AN: 152162 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

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: 0.0000147

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00106 AC: 163 AN: 154480 AF XY: 0.000733

Gnomad AFR exome AF: 0.0179

Gnomad AMR exome AF: 0.000730

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000335

Gnomad OTH exome AF: 0.000229

GnomAD4 exome AF: 0.000433 AC: 606 AN: 1398168 Hom.: 2 Cov.: 40 AF XY: 0.000365 AC XY: 252 AN XY: 689660

African (AFR) AF: 0.0164 AC: 517 AN: 31598

American (AMR) AF: 0.000784 AC: 28 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47992

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

European-Non Finnish (NFE) AF: 0.00000556 AC: 6 AN: 1078996

Other (OTH) AF: 0.000931 AC: 54 AN: 58024

GnomAD4 genome AF: 0.00464 AC: 707 AN: 152280 Hom.: 12 Cov.: 33 AF XY: 0.00445 AC XY: 331 AN XY: 74450

African (AFR) AF: 0.0164 AC: 682 AN: 41564

American (AMR) AF: 0.00150 AC: 23 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

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

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68016

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000455 Hom.: 0

Bravo AF: 0.00555

ESP6500AA AF: 0.0145 AC: 20

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00159 AC: 42

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 19, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.9
DANN	Uncertain	0.98
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.16
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.041
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.0090	D
Vest4		0.15
MVP		0.055
ClinPred		0.026	T
GERP RS		0.49
gMVP		0.54
Mutation Taster		=98/2	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: rs115672213; hg19: chr3-43074371;