NM_018652.5:c.979G>C

Variant names:

• chr15-72662383-G-C
• rs376161411
• NM_018652.5:c.979G>C

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.979G>C​(p.Ala327Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000233 in 1,392,594 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A327D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000079 (2 hom., cov: 20)
  • Exomes 𝑓: 0.00025 (74 hom.)
• Consequence: GOLGA6B NM_018652.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.259
• 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=0.1380657).
• BS2: High Homozygotes in GnomAd4 at 2 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.979G>C	p.Ala327Pro	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.979G>C	p.Ala327Pro	missense	Exon 11 of 18	ENSP00000408132.3	A6NDN3
	GOLGA6B	ENST00000909077.1		c.973G>C	p.Ala325Pro	missense	Exon 11 of 18	ENSP00000579136.1

Frequencies

GnomAD3 genomes AF: 0.0000790 AC: 10 AN: 126524 Hom.: 2 Cov.: 20

Gnomad AFR AF: 0.0000277

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: 0.000158

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000600 AC: 13 AN: 216714 AF XY: 0.0000769

Gnomad AFR exome AF: 0.000140

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: 0.000101

Gnomad OTH exome AF: 0.000187

GnomAD4 exome AF: 0.000248 AC: 314 AN: 1266070 Hom.: 74 Cov.: 36 AF XY: 0.000229 AC XY: 144 AN XY: 627638

African (AFR) AF: 0.0000966 AC: 3 AN: 31068

American (AMR) AF: 0.00 AC: 0 AN: 39864

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20880

East Asian (EAS) AF: 0.00 AC: 0 AN: 33840

South Asian (SAS) AF: 0.00 AC: 0 AN: 68818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45648

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4290

European-Non Finnish (NFE) AF: 0.000303 AC: 294 AN: 969478

Other (OTH) AF: 0.000326 AC: 17 AN: 52184

GnomAD4 genome AF: 0.0000790 AC: 10 AN: 126524 Hom.: 2 Cov.: 20 AF XY: 0.0000328 AC XY: 2 AN XY: 60980

African (AFR) AF: 0.0000277 AC: 1 AN: 36044

American (AMR) AF: 0.00 AC: 0 AN: 12656

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4096

South Asian (SAS) AF: 0.00 AC: 0 AN: 3324

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8342

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

European-Non Finnish (NFE) AF: 0.000158 AC: 9 AN: 56882

Other (OTH) AF: 0.00 AC: 0 AN: 1608

Alfa AF: 0.0000742 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000129 AC: 1

ExAC AF: 0.0000625 AC: 7

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	Uncertain	0.54
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.26
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.015
Sift	Benign	0.29	T
Sift4G	Benign	0.30	T
Polyphen		1.0	D
Vest4		0.19
MVP		0.076
ClinPred		0.054	T
GERP RS		0.37
Varity_R		0.25
gMVP		0.39
Mutation Taster		=95/5	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: rs376161411; hg19: chr15-72954724;