rs773392233

Variant names:

• chr15-72662363-C-G
• rs773392233
• NM_018652.5:c.959C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-72662363-C-G
• chr15-72662363-C-A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_018652.5(GOLGA6B):​c.959C>G​(p.Ser320Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000726 in 1,390,386 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000048 (1 hom., cov: 20)
  • Exomes 𝑓: 0.000075 (27 hom.)
• Consequence: GOLGA6B NM_018652.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.399
• Publications: 2 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11935368).
• BS2: High Homozygotes in GnomAdExome4 at 27 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.959C>G	p.Ser320Cys	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.959C>G	p.Ser320Cys	missense	Exon 11 of 18	ENSP00000408132.3	A6NDN3
	GOLGA6B	ENST00000909077.1		c.953C>G	p.Ser318Cys	missense	Exon 11 of 18	ENSP00000579136.1

Frequencies

GnomAD3 genomes AF: 0.0000476 AC: 6 AN: 126132 Hom.: 1 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000106

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000418 AC: 9 AN: 215332 AF XY: 0.0000516

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: 0.0000918

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000751 AC: 95 AN: 1264254 Hom.: 27 Cov.: 35 AF XY: 0.0000750 AC XY: 47 AN XY: 626586

African (AFR) AF: 0.00 AC: 0 AN: 31050

American (AMR) AF: 0.00 AC: 0 AN: 39812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20870

East Asian (EAS) AF: 0.00 AC: 0 AN: 33826

South Asian (SAS) AF: 0.00 AC: 0 AN: 68302

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4180

European-Non Finnish (NFE) AF: 0.0000971 AC: 94 AN: 968568

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

GnomAD4 genome AF: 0.0000476 AC: 6 AN: 126132 Hom.: 1 Cov.: 20 AF XY: 0.0000493 AC XY: 3 AN XY: 60794

African (AFR) AF: 0.00 AC: 0 AN: 35944

American (AMR) AF: 0.00 AC: 0 AN: 12616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.00 AC: 0 AN: 4100

South Asian (SAS) AF: 0.00 AC: 0 AN: 3312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.000106 AC: 6 AN: 56728

Other (OTH) AF: 0.00 AC: 0 AN: 1604

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000534 AC: 6

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	0.083
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	10
DANN	Benign	0.97
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.051	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.40
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.13
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.97	D
Vest4		0.13
MVP		0.061
ClinPred		0.12	T
GERP RS		-1.4
Varity_R		0.072
gMVP		0.11
Mutation Taster		=85/15	polymorphism

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: rs773392233; hg19: chr15-72954704; COSMIC: COSV101406965; COSMIC: COSV101406965;