15-72662363-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018652.5(GOLGA6B):​c.959C>A​(p.Ser320Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. S320C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0000063 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6B NM_018652.5 missense
• Clinical Significance: Not reported in ClinVar
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06639576).

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>A	p.Ser320Tyr	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>A	p.Ser320Tyr	missense	Exon 11 of 18	ENSP00000408132.3	A6NDN3
	GOLGA6B	ENST00000909077.1		c.953C>A	p.Ser318Tyr	missense	Exon 11 of 18	ENSP00000579136.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 126132 Hom.: 0 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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000929 AC: 2 AN: 215332 AF XY: 0.0000172

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000129

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000633 AC: 8 AN: 1264254 Hom.: 1 Cov.: 35 AF XY: 0.00000798 AC XY: 5 AN XY: 626586

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 0.0000591 AC: 2 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: 0.00000619 AC: 6 AN: 968568

Other (OTH) AF: 0.00 AC: 0 AN: 52104

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000588567), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 126132 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 AN: 56728

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

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000178 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	3.0
DANN	Benign	0.84
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.039	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.40
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.036
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.011	D
Polyphen		0.18	B
Vest4		0.14
MutPred		0.20		Gain of solvent accessibility (P = 0.1133)
MVP		0.055
ClinPred		0.21	T
GERP RS		-1.4
Varity_R		0.18
gMVP		0.18
Mutation Taster		=86/14	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: rs773392233; hg19: chr15-72954704; COSMIC: COSV69769992; COSMIC: COSV69769992;