chr15-72662506-C-T

Variant names:

• chr15-72662506-C-T
• rs577326920
• NM_018652.5:c.1102C>T

Variant summary

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

The NM_018652.5(GOLGA6B):​c.1102C>T​(p.Arg368Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.000024 (0 hom., cov: 20)
  • Exomes 𝑓: 0.000032 (6 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6B NM_018652.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.24
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032909423).

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.1102C>T	p.Arg368Trp	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.1102C>T	p.Arg368Trp	missense	Exon 11 of 18	ENSP00000408132.3	A6NDN3
	GOLGA6B	ENST00000909077.1		c.1096C>T	p.Arg366Trp	missense	Exon 11 of 18	ENSP00000579136.1

Frequencies

GnomAD3 genomes AF: 0.0000237 AC: 3 AN: 126700 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.0000279

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000242

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000175

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000430 AC: 8 AN: 186144 AF XY: 0.0000398

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000366

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000281

Gnomad FIN exome AF: 0.0000604

Gnomad NFE exome AF: 0.0000237

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000317 AC: 42 AN: 1323408 Hom.: 6 Cov.: 35 AF XY: 0.0000334 AC XY: 22 AN XY: 658444

African (AFR) AF: 0.00 AC: 0 AN: 31752

American (AMR) AF: 0.0000239 AC: 1 AN: 41808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23232

East Asian (EAS) AF: 0.000159 AC: 6 AN: 37812

South Asian (SAS) AF: 0.00 AC: 0 AN: 77730

European-Finnish (FIN) AF: 0.000122 AC: 6 AN: 49300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4352

European-Non Finnish (NFE) AF: 0.0000289 AC: 29 AN: 1002056

Other (OTH) AF: 0.00 AC: 0 AN: 55366

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000237 AC: 3 AN: 126824 Hom.: 0 Cov.: 20 AF XY: 0.0000327 AC XY: 2 AN XY: 61220

African (AFR) AF: 0.0000278 AC: 1 AN: 35932

American (AMR) AF: 0.00 AC: 0 AN: 12680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2660

East Asian (EAS) AF: 0.000243 AC: 1 AN: 4122

South Asian (SAS) AF: 0.00 AC: 0 AN: 3298

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 248

European-Non Finnish (NFE) AF: 0.0000175 AC: 1 AN: 56996

Other (OTH) AF: 0.00 AC: 0 AN: 1656

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000981 AC: 1

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	-0.52	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.5
DANN	Benign	0.96
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L
PhyloP100		-2.2
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.043
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.088	T
Polyphen		0.0030	B
Vest4		0.14
MVP		0.014
ClinPred		0.11	T
Varity_R		0.051
gMVP		0.37
Mutation Taster		=92/8	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: rs577326920; hg19: chr15-72954847;