9-86035592-T-G

Position:

• chr9-86035592-T-G

Variant summary

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

The NM_016548.4(GOLM1):​c.791A>C​(p.Glu264Ala) 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 1,453,664 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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: 1.26

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.067278385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLM1	NM_016548.4	c.791A>C	p.Glu264Ala	missense_variant	8/10	ENST00000388712.7	NP_057632.2
GOLM1	NM_177937.3	c.791A>C	p.Glu264Ala	missense_variant	8/10		NP_808800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLM1	ENST00000388712.7	c.791A>C	p.Glu264Ala	missense_variant	8/10	1	NM_016548.4	ENSP00000373364.3
GOLM1	ENST00000388711.7	c.791A>C	p.Glu264Ala	missense_variant	8/10	1		ENSP00000373363.3
GOLM1	ENST00000257504.10	n.790A>C		non_coding_transcript_exon_variant	7/7	5
GOLM1	ENST00000464314.1	n.500A>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453664 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 723544

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2024

The c.791A>C (p.E264A) alteration is located in exon 8 (coding exon 7) of the GOLM1 gene. This alteration results from a A to C substitution at nucleotide position 791, causing the glutamic acid (E) at amino acid position 264 to be replaced by an alanine (A). 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	0.098
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.069	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.27	.;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.067	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.037
Sift	Benign	0.23	T;T
Sift4G	Benign	0.072	T;T
Polyphen		0.0080	B;B
Vest4		0.28
MutPred		0.23		Loss of solvent accessibility (P = 0.3473);Loss of solvent accessibility (P = 0.3473);
MVP		0.16
MPC		0.14
ClinPred		0.097	T
GERP RS		-0.35
Varity_R		0.044
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr9-88650507;