chr15-72662270-C-T

Variant names:

• chr15-72662270-C-T
• rs369108064
• NM_018652.5:c.866C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_018652.5(GOLGA6B):​c.866C>T​(p.Ala289Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000881 in 1,384,176 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000074 (2 hom., cov: 19)
  • Exomes 𝑓: 0.000089 (33 hom.)
• Consequence: GOLGA6B NM_018652.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.246
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.025268495).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.866C>T	p.Ala289Val	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.866C>T	p.Ala289Val	missense	Exon 11 of 18	ENSP00000408132.3	A6NDN3
	GOLGA6B	ENST00000909077.1		c.860C>T	p.Ala287Val	missense	Exon 11 of 18	ENSP00000579136.1

Frequencies

GnomAD3 genomes AF: 0.0000745 AC: 9 AN: 120870 Hom.: 2 Cov.: 19

Gnomad AFR AF: 0.0000291

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000857

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000127

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000176 AC: 38 AN: 215662 AF XY: 0.000120

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000288

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000379

Gnomad NFE exome AF: 0.000205

Gnomad OTH exome AF: 0.000188

GnomAD4 exome AF: 0.0000894 AC: 113 AN: 1263306 Hom.: 33 Cov.: 36 AF XY: 0.0000799 AC XY: 50 AN XY: 626028

African (AFR) AF: 0.00 AC: 0 AN: 30986

American (AMR) AF: 0.000302 AC: 12 AN: 39670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20764

East Asian (EAS) AF: 0.0000881 AC: 3 AN: 34058

South Asian (SAS) AF: 0.000205 AC: 14 AN: 68370

European-Finnish (FIN) AF: 0.000352 AC: 16 AN: 45468

Middle Eastern (MID) AF: 0.000840 AC: 3 AN: 3570

European-Non Finnish (NFE) AF: 0.0000589 AC: 57 AN: 968338

Other (OTH) AF: 0.000154 AC: 8 AN: 52082

GnomAD4 genome AF: 0.0000745 AC: 9 AN: 120870 Hom.: 2 Cov.: 19 AF XY: 0.0000519 AC XY: 3 AN XY: 57846

African (AFR) AF: 0.0000291 AC: 1 AN: 34418

American (AMR) AF: 0.0000857 AC: 1 AN: 11664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2494

East Asian (EAS) AF: 0.00 AC: 0 AN: 3964

South Asian (SAS) AF: 0.00 AC: 0 AN: 3094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.000127 AC: 7 AN: 55156

Other (OTH) AF: 0.00 AC: 0 AN: 1538

Alfa AF: 0.00 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000267 AC: 2

ExAC AF: 0.000192 AC: 21

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	14
DANN	Benign	0.56
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0098	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.25
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.079
Sift	Benign	0.20	T
Sift4G	Benign	0.19	T
Polyphen		0.0	B
Vest4		0.073
MVP		0.014
ClinPred		0.0099	T
GERP RS		-1.4
Varity_R		0.025
gMVP		0.15
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs369108064; hg19: chr15-72954611; COSMIC: COSV69769787; COSMIC: COSV69769787;