1-204201759-C-A

Variant names:

• chr1-204201759-C-A
• rs1658966355
• NM_198447.2:c.170G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198447.2(GOLT1A):​c.170G>T​(p.Trp57Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GOLT1A NM_198447.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.410

Genes affected

GOLT1A (HGNC:24766): (golgi transport 1A) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport. Located in Golgi apparatus subcompartment; endoplasmic reticulum; and nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16765842).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLT1A	NM_198447.2	c.170G>T	p.Trp57Leu	missense_variant	Exon 3 of 5	ENST00000308302.4	NP_940849.1
GOLT1A	XM_017000314.2	c.170G>T	p.Trp57Leu	missense_variant	Exon 3 of 5		XP_016855803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLT1A	ENST00000308302.4	c.170G>T	p.Trp57Leu	missense_variant	Exon 3 of 5	1	NM_198447.2	ENSP00000308535.3
GOLT1A	ENST00000475517.1	n.-58G>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.170G>T (p.W57L) alteration is located in exon 3 (coding exon 3) of the GOLT1A gene. This alteration results from a G to T substitution at nucleotide position 170, causing the tryptophan (W) at amino acid position 57 to be replaced by a leucine (L). 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	0.078
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	3.3
DANN	Benign	0.46
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.0	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.054
Sift	Benign	0.61	T
Sift4G	Benign	0.36	T
Polyphen		0.0040	B
Vest4		0.33
MutPred		0.44		Loss of MoRF binding (P = 0.0436);
MVP		0.067
MPC		0.21
ClinPred		0.094	T
GERP RS		0.90
Varity_R		0.056
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1658966355; hg19: chr1-204170887;