15-72662276-C-G

Variant names:

• chr15-72662276-C-G
• rs746768374
• NM_018652.5:c.872C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018652.5(GOLGA6B):​c.872C>G​(p.Pro291Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000237 in 1,263,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P291L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: GOLGA6B NM_018652.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.383
• Publications: 0 publications found

Genes affected

GOLGA6B (HGNC:32205): (golgin A6 family member B) This gene is found in a large, low copy repeat sequence or duplicon that is found in multiple copies, which are greater than 90% similar, on chromosome 15. Duplicons are associated with deletions, inversions and other chromosomal rearrangements that underlie genomic disease. This gene is a member of the golgin gene family, whose protein products localize to the Golgi apparatus. The majority of the related gene copies are thought to be transcribed pseudogenes. It is not known whether this gene is a pseudogene or if it encodes a golgin protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2519276).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018652.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6B	NM_018652.5	MANE Select	c.872C>G	p.Pro291Arg	missense	Exon 11 of 18	NP_061122.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6B	ENST00000421285.4	TSL:1 MANE Select	c.872C>G	p.Pro291Arg	missense	Exon 11 of 18	ENSP00000408132.3	A6NDN3
	GOLGA6B	ENST00000909077.1		c.866C>G	p.Pro289Arg	missense	Exon 11 of 18	ENSP00000579136.1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD2 exomes AF: 0.00000465 AC: 1 AN: 215050 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000237 AC: 3 AN: 1263766 Hom.: 0 Cov.: 36 AF XY: 0.00000160 AC XY: 1 AN XY: 626260

African (AFR) AF: 0.00 AC: 0 AN: 30996

American (AMR) AF: 0.00 AC: 0 AN: 39696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20834

East Asian (EAS) AF: 0.00 AC: 0 AN: 34134

South Asian (SAS) AF: 0.0000292 AC: 2 AN: 68422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3638

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 968472

Other (OTH) AF: 0.0000192 AC: 1 AN: 52104

GnomAD4 genome Cov.: 19

ExAC AF: 0.00000911 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.074	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		0.38
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-6.5	D
REVEL	Benign	0.063
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.11
MutPred		0.36		Gain of MoRF binding (P = 0.0106)
MVP		0.17
ClinPred		0.74	D
GERP RS		0.69
Varity_R		0.30
gMVP		0.15
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs746768374; hg19: chr15-72954617;