chr9-86035580-T-A

Position:

• chr9-86035580-T-A

Variant summary

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

The NM_016548.4(GOLM1):​c.803A>T​(p.Asp268Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.133

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=0.06639746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLM1	NM_016548.4	c.803A>T	p.Asp268Val	missense_variant	8/10	ENST00000388712.7	NP_057632.2
GOLM1	NM_177937.3	c.803A>T	p.Asp268Val	missense_variant	8/10		NP_808800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLM1	ENST00000388712.7	c.803A>T	p.Asp268Val	missense_variant	8/10	1	NM_016548.4	ENSP00000373364.3
GOLM1	ENST00000388711.7	c.803A>T	p.Asp268Val	missense_variant	8/10	1		ENSP00000373363.3
GOLM1	ENST00000464314.1	n.512A>T		non_coding_transcript_exon_variant	2/2	2
GOLM1	ENST00000257504.10	n.*8A>T		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455200 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 724226

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: 0.0000209

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

Nov 11, 2024

The c.803A>T (p.D268V) alteration is located in exon 8 (coding exon 7) of the GOLM1 gene. This alteration results from a A to T substitution at nucleotide position 803, causing the aspartic acid (D) at amino acid position 268 to be replaced by a valine (V). 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	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.073	T;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.40	.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.066	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.70	N;N
REVEL	Benign	0.064
Sift	Benign	0.058	T;T
Sift4G	Uncertain	0.038	D;D
Polyphen		0.22	B;B
Vest4		0.21
MutPred		0.28		Loss of solvent accessibility (P = 0.1279);Loss of solvent accessibility (P = 0.1279);
MVP		0.25
MPC		0.20
ClinPred		0.15	T
GERP RS		-1.4
Varity_R		0.044
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr9-88650495;