9-86035556-C-T

Variant names:

• chr9-86035556-C-T
• rs749034411
• NM_016548.4:c.827G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_016548.4(GOLM1):​c.827G>A​(p.Arg276Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,610,550 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: GOLM1 NM_016548.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.49

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]

ACMG classification

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=0.023302436).
• BP6: Variant 9-86035556-C-T is Benign according to our data. Variant chr9-86035556-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2300105.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLM1	NM_016548.4	c.827G>A	p.Arg276Gln	missense_variant	Exon 8 of 10	ENST00000388712.7	NP_057632.2
GOLM1	NM_177937.3	c.827G>A	p.Arg276Gln	missense_variant	Exon 8 of 10		NP_808800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLM1	ENST00000388712.7	c.827G>A	p.Arg276Gln	missense_variant	Exon 8 of 10	1	NM_016548.4	ENSP00000373364.3
GOLM1	ENST00000388711.7	c.827G>A	p.Arg276Gln	missense_variant	Exon 8 of 10	1		ENSP00000373363.3
GOLM1	ENST00000464314.1	n.536G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
GOLM1	ENST00000257504.10	n.*32G>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 151920 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.0000161 AC: 4 AN: 249074 Hom.: 0 AF XY: 0.0000222 AC XY: 3 AN XY: 134902

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1458630 Hom.: 0 Cov.: 34 AF XY: 0.0000179 AC XY: 13 AN XY: 725818

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151920 Hom.: 0 Cov.: 29 AF XY: 0.0000269 AC XY: 2 AN XY: 74214

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000479

Bravo AF: 0.0000189

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jul 08, 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	0.064
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.0020
DANN	Benign	0.93
DEOGEN2	Benign	0.039	T;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0065	N
LIST_S2	Benign	0.61	.;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.023	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.38	N;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	0.20	N;N
REVEL	Benign	0.0090
Sift	Benign	0.63	T;T
Sift4G	Benign	0.55	T;T
Polyphen		0.0	B;B
Vest4		0.035
MutPred		0.19		Loss of MoRF binding (P = 0.3743);Loss of MoRF binding (P = 0.3743);
MVP		0.095
MPC		0.15
ClinPred		0.026	T
GERP RS		-8.8
Varity_R		0.011
gMVP		0.070

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: rs749034411; hg19: chr9-88650471;