chr15-72662467-C-T

Variant names:

• chr15-72662467-C-T
• rs376212280
• NM_018652.5:c.1063C>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.1063C>T​(p.Arg355Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,401,916 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00040 (8 hom., cov: 20)
  • Exomes 𝑓: 0.00011 (37 hom.)
• Consequence: GOLGA6B NM_018652.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.53
• Publications: 1 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=0.028002828).
• BS2: High Homozygotes in GnomAd4 at 8 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.1063C>T	p.Arg355Trp	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.1063C>T	p.Arg355Trp	missense	Exon 11 of 18	ENSP00000408132.3	A6NDN3
	GOLGA6B	ENST00000909077.1		c.1057C>T	p.Arg353Trp	missense	Exon 11 of 18	ENSP00000579136.1

Frequencies

GnomAD3 genomes AF: 0.000396 AC: 50 AN: 126298 Hom.: 8 Cov.: 20

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000635

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000302

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000527

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000148 AC: 32 AN: 215966 AF XY: 0.000111

Gnomad AFR exome AF: 0.000778

Gnomad AMR exome AF: 0.000321

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000917

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000114 AC: 145 AN: 1275500 Hom.: 37 Cov.: 35 AF XY: 0.000114 AC XY: 72 AN XY: 632974

African (AFR) AF: 0.000675 AC: 21 AN: 31092

American (AMR) AF: 0.000298 AC: 12 AN: 40302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21018

East Asian (EAS) AF: 0.00 AC: 0 AN: 34438

South Asian (SAS) AF: 0.0000421 AC: 3 AN: 71282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45942

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4428

European-Non Finnish (NFE) AF: 0.000107 AC: 104 AN: 974328

Other (OTH) AF: 0.0000949 AC: 5 AN: 52670

GnomAD4 genome AF: 0.000396 AC: 50 AN: 126416 Hom.: 8 Cov.: 20 AF XY: 0.000442 AC XY: 27 AN XY: 61098

African (AFR) AF: 0.00106 AC: 38 AN: 35906

American (AMR) AF: 0.000634 AC: 8 AN: 12610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2662

East Asian (EAS) AF: 0.00 AC: 0 AN: 4062

South Asian (SAS) AF: 0.000302 AC: 1 AN: 3312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000527 AC: 3 AN: 56924

Other (OTH) AF: 0.00 AC: 0 AN: 1644

Alfa AF: 0.000169 Hom.: 1

ESP6500AA AF: 0.000242 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000130 AC: 14

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	0.098
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.2
DANN	Benign	0.89
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L
PhyloP100		-2.5
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.024
Sift	Benign	0.088	T
Sift4G	Uncertain	0.054	T
Polyphen		0.0	B
Vest4		0.20
MVP		0.061
ClinPred		0.034	T
Varity_R		0.046
gMVP		0.26
Mutation Taster		=94/6	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: rs376212280; hg19: chr15-72954808; COSMIC: COSV101406901; COSMIC: COSV101406901;