chr9-86036426-C-A

Variant names:

• chr9-86036426-C-A
• rs141860390
• NM_016548.4:c.679G>T

Variant summary

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

The NM_016548.4(GOLM1):​c.679G>T​(p.Val227Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V227M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GOLM1 NM_016548.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059033692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLM1	NM_016548.4	c.679G>T	p.Val227Leu	missense_variant	Exon 7 of 10	ENST00000388712.7	NP_057632.2
GOLM1	NM_177937.3	c.679G>T	p.Val227Leu	missense_variant	Exon 7 of 10		NP_808800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLM1	ENST00000388712.7	c.679G>T	p.Val227Leu	missense_variant	Exon 7 of 10	1	NM_016548.4	ENSP00000373364.3
GOLM1	ENST00000388711.7	c.679G>T	p.Val227Leu	missense_variant	Exon 7 of 10	1		ENSP00000373363.3
GOLM1	ENST00000257504.10	n.678G>T		non_coding_transcript_exon_variant	Exon 6 of 7	5
GOLM1	ENST00000464314.1	n.388G>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.057
DANN	Benign	0.45
DEOGEN2	Benign	0.067	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.37	.;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.059	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.019
Sift	Benign	0.21	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.0	B;B
Vest4		0.14
MutPred		0.17		Loss of methylation at K224 (P = 0.0729);Loss of methylation at K224 (P = 0.0729);
MVP		0.17
MPC		0.13
ClinPred		0.029	T
GERP RS		-0.050
Varity_R		0.047
gMVP		0.096

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: rs141860390; hg19: chr9-88651341;