9-86035593-C-T

Variant names:

• chr9-86035593-C-T
• NM_016548.4:c.790G>A

Variant summary

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

The NM_016548.4(GOLM1):​c.790G>A​(p.Glu264Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E264A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GOLM1 NM_016548.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96

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 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=0.15357912).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLM1	NM_016548.4	c.790G>A	p.Glu264Lys	missense_variant	Exon 8 of 10	ENST00000388712.7	NP_057632.2
GOLM1	NM_177937.3	c.790G>A	p.Glu264Lys	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.790G>A	p.Glu264Lys	missense_variant	Exon 8 of 10	1	NM_016548.4	ENSP00000373364.3
GOLM1	ENST00000388711.7	c.790G>A	p.Glu264Lys	missense_variant	Exon 8 of 10	1		ENSP00000373363.3
GOLM1	ENST00000257504.10	n.789G>A		non_coding_transcript_exon_variant	Exon 7 of 7	5
GOLM1	ENST00000464314.1	n.499G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453078 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 723284

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.790G>A (p.E264K) alteration is located in exon 8 (coding exon 7) of the GOLM1 gene. This alteration results from a G to A substitution at nucleotide position 790, causing the glutamic acid (E) at amino acid position 264 to be replaced by a lysine (K). 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	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.35	.;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.86	N;N
REVEL	Benign	0.080
Sift	Benign	0.45	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.72	P;P
Vest4		0.41
MutPred		0.26		Gain of ubiquitination at E264 (P = 0.0014);Gain of ubiquitination at E264 (P = 0.0014);
MVP		0.53
MPC		0.15
ClinPred		0.40	T
GERP RS		3.7
Varity_R		0.075
gMVP		0.18

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: chr9-88650508;