15-72662496-C-G

Variant names:

• chr15-72662496-C-G
• rs375343704
• NM_018652.5:c.1092C>G

Variant summary

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

The NM_018652.5(GOLGA6B):​c.1092C>G​(p.Asn364Lys) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N364N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6B NM_018652.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• 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=0.05261728).

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.1092C>G	p.Asn364Lys	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.1092C>G	p.Asn364Lys	missense	Exon 11 of 18	ENSP00000408132.3	A6NDN3
	GOLGA6B	ENST00000909077.1		c.1086C>G	p.Asn362Lys	missense	Exon 11 of 18	ENSP00000579136.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.60e-7 AC: 1 AN: 1315464 Hom.: 0 Cov.: 35 AF XY: 0.00000153 AC XY: 1 AN XY: 654356

African (AFR) AF: 0.00 AC: 0 AN: 31648

American (AMR) AF: 0.00 AC: 0 AN: 41626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22806

East Asian (EAS) AF: 0.00 AC: 0 AN: 37322

South Asian (SAS) AF: 0.00 AC: 0 AN: 77350

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4412

European-Non Finnish (NFE) AF: 0.00000100 AC: 1 AN: 996778

Other (OTH) AF: 0.00 AC: 0 AN: 54918

GnomAD4 genome Cov.: 20

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.021
DANN	Benign	0.78
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.51	N
PhyloP100		-1.5
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.014
Sift	Benign	0.16	T
Sift4G	Benign	0.74	T
Polyphen		0.0010	B
Vest4		0.092
MutPred		0.39		Gain of ubiquitination at N364 (P = 0.0155)
MVP		0.014
ClinPred		0.071	T
Varity_R		0.072
gMVP		0.27

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: rs375343704; hg19: chr15-72954837;