1-204201668-C-G

Variant names:

• chr1-204201668-C-G
• NM_198447.2:c.261G>C

Variant summary

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

The NM_198447.2(GOLT1A):​c.261G>C​(p.Met87Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GOLT1A NM_198447.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.18

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLT1A	NM_198447.2	c.261G>C	p.Met87Ile	missense_variant	Exon 3 of 5	ENST00000308302.4	NP_940849.1
GOLT1A	XM_017000314.2	c.261G>C	p.Met87Ile	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.261G>C	p.Met87Ile	missense_variant	Exon 3 of 5	1	NM_198447.2	ENSP00000308535.3
GOLT1A	ENST00000475517.1	n.34G>C		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.261G>C (p.M87I) alteration is located in exon 3 (coding exon 3) of the GOLT1A gene. This alteration results from a G to C substitution at nucleotide position 261, causing the methionine (M) at amino acid position 87 to be replaced by an isoleucine (I). 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	0.32
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.31	T
Eigen	Benign	0.030
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.26
Sift	Benign	0.11	T
Sift4G	Benign	0.29	T
Polyphen		0.34	B
Vest4		0.44
MutPred		0.74		Gain of catalytic residue at M87 (P = 0.0852);
MVP		0.24
MPC		0.15
ClinPred		0.82	D
GERP RS		5.5
Varity_R		0.41
gMVP		0.92

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-204170796;