15-23364417-T-G

Variant names:

• chr15-23364417-T-G
• rs4036680
• NM_001395373.1:c.1461T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001395373.1(GOLGA8S):​c.1461T>G​(p.Ile487Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,604,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 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. I487I) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GOLGA8S NM_001395373.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• Publications: 0 publications found

Genes affected

GOLGA8S (HGNC:44409): (golgin A8 family member S) Predicted to be involved in Golgi organization. Predicted to be active in Golgi cis cisterna; Golgi cisterna membrane; and cis-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

LOC105370726 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31542414).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395373.1. 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
	GOLGA8S	NM_001395373.1	MANE Select	c.1461T>G	p.Ile487Met	missense	Exon 16 of 19	NP_001382302.1	H3BPF8
	GOLGA8S	NM_001355465.2		c.783T>G	p.Ile261Met	missense	Exon 15 of 18	NP_001342394.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA8S	ENST00000562295.3	TSL:5 MANE Select	c.1461T>G	p.Ile487Met	missense	Exon 16 of 19	ENSP00000455298.2	H3BPF8
	GOLGA8S	ENST00000604046.1	TSL:1	n.1796T>G		non_coding_transcript_exon	Exon 15 of 18

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151772 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000726

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000832 AC: 2 AN: 240282 AF XY: 0.00000762

Gnomad AFR exome AF: 0.000137

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1452604 Hom.: 0 Cov.: 47 AF XY: 0.00 AC XY: 0 AN XY: 722780

African (AFR) AF: 0.0000299 AC: 1 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 85910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45404

Middle Eastern (MID) AF: 0.000183 AC: 1 AN: 5478

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111560

Other (OTH) AF: 0.0000166 AC: 1 AN: 60270

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151772 Hom.: 0 Cov.: 29 AF XY: 0.0000135 AC XY: 1 AN XY: 74116

African (AFR) AF: 0.0000726 AC: 3 AN: 41340

American (AMR) AF: 0.00 AC: 0 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67910

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000167 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	15
DANN	Benign	0.35
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.32	T
PhyloP100		0.30
PROVEAN	Benign	-1.7	N
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.010	D
Vest4		0.42
MVP		0.80
MPC		1.4
GERP RS		-0.35
Varity_R		0.14
gMVP		0.20

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: rs4036680; hg19: chr15-23609564;