Genetic Variant GOLT1A:p.Arg123Gln (chr1-204198489-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_198447.2(GOLT1A):c.368G>A(p.Arg123Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000986 in 1,613,214 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 (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000097 ( 0 hom. )

Consequence

GOLT1A
NM_198447.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.87

Variant links:

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]

GOLT1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008010268).

BP6

Variant 1-204198489-C-T is Benign according to our data. Variant chr1-204198489-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2373937.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLT1A	NM_198447.2 link	c.368G>A	p.Arg123Gln	missense_variant	Exon 5 of 5	ENST00000308302.4	NP_940849.1	Q6ZVE7
GOLT1A	XM_017000314.2 link	c.361-151G>A		intron_variant	Intron 4 of 4		XP_016855803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLT1A	ENST00000308302.4 link	c.368G>A	p.Arg123Gln	missense_variant	Exon 5 of 5	1	NM_198447.2	ENSP00000308535.3		Q6ZVE7

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000161

AC:

AN:

248562

Hom.:

AF XY:

0.0000743

AC XY:

AN XY:

134570

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000554

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000382

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000538

Gnomad OTH exome

AF:

0.000821

GnomAD4 exome

AF:

0.0000965

AC:

141

AN:

1460954

Hom.:

Cov.:

AF XY:

0.0000688

AC XY:

AN XY:

726790

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000494

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000990

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000118

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000103

Hom.:

Bravo

AF:

0.000215

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000198

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

May 27, 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

0.062

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.65

CADD

Benign

4.4

DANN

Benign

0.95

DEOGEN2

Benign

0.16

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.60

M_CAP

Benign

0.0048

MetaRNN

Benign

0.0080

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.24

PROVEAN

Benign

0.74

REVEL

Benign

0.079

Sift

Benign

0.21

Sift4G

Benign

0.50

Polyphen

0.0010

Vest4

0.054

MVP

0.030

MPC

0.13

ClinPred

0.033

GERP RS

-7.0

Varity_R

0.025

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over