15-72662276-C-T

Variant names:

• chr15-72662276-C-T
• rs746768374
• NM_018652.5:c.872C>T

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.872C>T​(p.Pro291Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,386,926 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000049 (0 hom., cov: 19)
  • Exomes 𝑓: 0.000044 (12 hom.)
• Consequence: GOLGA6B NM_018652.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.383
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15825525).
• BS2: High Homozygotes in GnomAdExome4 at 12 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.872C>T	p.Pro291Leu	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.872C>T	p.Pro291Leu	missense	Exon 11 of 18	ENSP00000408132.3	A6NDN3
	GOLGA6B	ENST00000909077.1		c.866C>T	p.Pro289Leu	missense	Exon 11 of 18	ENSP00000579136.1

Frequencies

GnomAD3 genomes AF: 0.0000488 AC: 6 AN: 123040 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.0000572

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000245

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00407

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000107 AC: 23 AN: 215050 AF XY: 0.0000602

Gnomad AFR exome AF: 0.000356

Gnomad AMR exome AF: 0.000417

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000513

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000443 AC: 56 AN: 1263766 Hom.: 12 Cov.: 36 AF XY: 0.0000511 AC XY: 32 AN XY: 626260

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

African (AFR) AF: 0.000323 AC: 10 AN: 30996

American (AMR) AF: 0.000403 AC: 16 AN: 39696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20834

East Asian (EAS) AF: 0.00 AC: 0 AN: 34134

South Asian (SAS) AF: 0.00 AC: 0 AN: 68422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45470

Middle Eastern (MID) AF: 0.00165 AC: 6 AN: 3638

European-Non Finnish (NFE) AF: 0.0000103 AC: 10 AN: 968472

Other (OTH) AF: 0.000269 AC: 14 AN: 52104

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000587752), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000487 AC: 6 AN: 123160 Hom.: 0 Cov.: 19 AF XY: 0.0000506 AC XY: 3 AN XY: 59330

African (AFR) AF: 0.0000571 AC: 2 AN: 35056

American (AMR) AF: 0.000245 AC: 3 AN: 12250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2532

East Asian (EAS) AF: 0.00 AC: 0 AN: 4038

South Asian (SAS) AF: 0.00 AC: 0 AN: 3202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8034

Middle Eastern (MID) AF: 0.00431 AC: 1 AN: 232

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 55578

Other (OTH) AF: 0.00 AC: 0 AN: 1590

Alfa AF: 0.0000843 Hom.: 0

ExAC AF: 0.0000820 AC: 9

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	0.10
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		0.38
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-7.2	D
REVEL	Benign	0.069
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.086
MVP		0.15
ClinPred		0.20	T
GERP RS		0.69
Varity_R		0.20
gMVP		0.20
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs746768374; hg19: chr15-72954617;