chr9-86046538-C-G

Position:

• chr9-86046538-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016548.4(GOLM1):​c.399G>C​(p.Arg133Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00296 in 1,613,242 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (41 hom.)
• Consequence: GOLM1 NM_016548.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.302

Genes affected

GOLM1 (HGNC:15451): (golgi membrane protein 1) The Golgi complex plays a key role in the sorting and modification of proteins exported from the endoplasmic reticulum. The protein encoded by this gene is a type II Golgi transmembrane protein. It processes proteins synthesized in the rough endoplasmic reticulum and assists in the transport of protein cargo through the Golgi apparatus. The expression of this gene has been observed to be upregulated in response to viral infection. Alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Sep 2009]

GOLM1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006363988).
• BP6: Variant 9-86046538-C-G is Benign according to our data. Variant chr9-86046538-C-G is described in ClinVar as [Benign]. Clinvar id is 2659288.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00304 (4443/1460924) while in subpopulation SAS AF= 0.016 (1374/86126). AF 95% confidence interval is 0.0153. There are 41 homozygotes in gnomad4_exome. There are 2541 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLM1	NM_016548.4	c.399G>C	p.Arg133Ser	missense_variant	5/10	ENST00000388712.7	NP_057632.2
GOLM1	NM_177937.3	c.399G>C	p.Arg133Ser	missense_variant	5/10		NP_808800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLM1	ENST00000388712.7	c.399G>C	p.Arg133Ser	missense_variant	5/10	1	NM_016548.4	ENSP00000373364.3

Frequencies

GnomAD3 genomes AF: 0.00219 AC: 334 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000941

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00206

Gnomad OTH AF: 0.00525

GnomAD3 exomes AF: 0.00370 AC: 925 AN: 250268 Hom.: 14 AF XY: 0.00450 AC XY: 609 AN XY: 135234

Gnomad AFR exome AF: 0.000618

Gnomad AMR exome AF: 0.00258

Gnomad ASJ exome AF: 0.00856

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0153

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00217

Gnomad OTH exome AF: 0.00442

GnomAD4 exome AF: 0.00304 AC: 4443 AN: 1460924 Hom.: 41 Cov.: 29 AF XY: 0.00350 AC XY: 2541 AN XY: 726780

Gnomad4 AFR exome AF: 0.000598

Gnomad4 AMR exome AF: 0.00257

Gnomad4 ASJ exome AF: 0.00793

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0160

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00222

Gnomad4 OTH exome AF: 0.00335

GnomAD4 genome AF: 0.00221 AC: 337 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.00201 AC XY: 150 AN XY: 74484

Gnomad4 AFR AF: 0.000962

Gnomad4 AMR AF: 0.00359

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00206

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00236 Hom.: 1

Bravo AF: 0.00228

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00467 AC: 18

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00198 AC: 17

ExAC AF: 0.00396 AC: 481

Asia WGS AF: 0.00635 AC: 23 AN: 3478

EpiCase AF: 0.00294

EpiControl AF: 0.00226

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

GOLM1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.72	.;T
MetaRNN	Benign	0.0064	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.081
Sift	Benign	0.15	T;T
Sift4G	Benign	0.092	T;T
Polyphen		0.010	B;B
Vest4		0.22
MutPred		0.18		Loss of MoRF binding (P = 0.0064);Loss of MoRF binding (P = 0.0064);
MVP		0.22
MPC		0.15
ClinPred		0.012	T
GERP RS		0.30
Varity_R		0.14
gMVP		0.053

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

LitVar

Other links and lift over

dbSNP: rs140984957; hg19: chr9-88661453; COSMIC: COSV105083554;