3-43032616-T-C

Variant names:

• chr3-43032616-T-C
• NM_001129908.3:c.353T>C

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.353T>C​(p.Val118Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,378 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 (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GASK1A NM_001129908.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.492
• 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=0.045989186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GASK1A	NM_001129908.3	c.353T>C	p.Val118Ala	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.353T>C	p.Val118Ala	missense_variant	Exon 2 of 5	5	NM_001129908.3	ENSP00000407301.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399378 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 690192

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 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: 79232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078926

Other (OTH) AF: 0.00 AC: 0 AN: 58010

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.353T>C (p.V118A) alteration is located in exon 2 (coding exon 2) of the FAM198A gene. This alteration results from a T to C substitution at nucleotide position 353, causing the valine (V) at amino acid position 118 to be replaced by an alanine (A). 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	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.6
DANN	Benign	0.97
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.0096	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.49
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.014
Sift	Benign	0.16	T
Sift4G	Benign	0.21	T
Vest4		0.042
MutPred		0.23		Gain of glycosylation at T123 (P = 0.0188);
MVP		0.014
ClinPred		0.12	T
GERP RS		2.2
gMVP		0.17
Mutation Taster		=97/3	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

hg19: chr3-43074108;