15-72661493-G-T

Variant names:

• chr15-72661493-G-T
• rs1288129339
• NM_018652.5:c.686G>T

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.686G>T​(p.Arg229Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R229Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000026 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6B NM_018652.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.34
• 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=0.14594594).

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.686G>T	p.Arg229Leu	missense	Exon 9 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.686G>T	p.Arg229Leu	missense	Exon 9 of 18	ENSP00000408132.3	A6NDN3
	GOLGA6B	ENST00000909077.1		c.680G>T	p.Arg227Leu	missense	Exon 9 of 18	ENSP00000579136.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000260 AC: 3 AN: 1155964 Hom.: 0 Cov.: 18 AF XY: 0.00000342 AC XY: 2 AN XY: 584302

African (AFR) AF: 0.00 AC: 0 AN: 26740

American (AMR) AF: 0.00 AC: 0 AN: 40648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23354

East Asian (EAS) AF: 0.00 AC: 0 AN: 38364

South Asian (SAS) AF: 0.00 AC: 0 AN: 79254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3576

European-Non Finnish (NFE) AF: 0.00000350 AC: 3 AN: 856510

Other (OTH) AF: 0.00 AC: 0 AN: 50308

GnomAD4 genome Cov.: 21

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Benign	0.67
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.21	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		4.3
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.18
Sift	Benign	0.19	T
Sift4G	Uncertain	0.039	D
Polyphen		0.034	B
Vest4		0.45
MutPred		0.34		Loss of disorder (P = 0.0521)
MVP		0.030
ClinPred		0.70	D
GERP RS		-0.78
Varity_R		0.14
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1288129339; hg19: chr15-72953834;