15-72662452-G-C

Variant names:

• chr15-72662452-G-C
• rs1214069745
• NM_018652.5:c.1048G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018652.5(GOLGA6B):​c.1048G>C​(p.Glu350Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000158 in 1,266,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: GOLGA6B NM_018652.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.43

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05201456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA6B	NM_018652.5	c.1048G>C	p.Glu350Gln	missense_variant	Exon 11 of 18	ENST00000421285.4	NP_061122.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA6B	ENST00000421285.4	c.1048G>C	p.Glu350Gln	missense_variant	Exon 11 of 18	1	NM_018652.5	ENSP00000408132.3

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD3 exomes AF: 0.00000921 AC: 2 AN: 217176 Hom.: 0 AF XY: 0.0000171 AC XY: 2 AN XY: 117284

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000638

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000158 AC: 2 AN: 1266760 Hom.: 0 Cov.: 36 AF XY: 0.00000318 AC XY: 2 AN XY: 628026

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000503

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 28, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1048G>C (p.E350Q) alteration is located in exon 11 (coding exon 11) of the GOLGA6B gene. This alteration results from a G to C substitution at nucleotide position 1048, causing the glutamic acid (E) at amino acid position 350 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.9
DANN	Benign	0.56
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.46	N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.024
Sift	Benign	0.24	T
Sift4G	Benign	0.20	T
Polyphen		0.17	B
Vest4		0.037
MutPred		0.32		Gain of MoRF binding (P = 0.0245);
MVP		0.030
ClinPred		0.045	T
GERP RS		0.37
Varity_R		0.050
gMVP		0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs1214069745; hg19: chr15-72954793;