NM_001395373.1:c.818C>T

Variant names:

• chr15-23360525-C-T
• rs530525459
• NM_001395373.1:c.818C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001395373.1(GOLGA8S):​c.818C>T​(p.Ser273Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (27 hom., cov: 27)
  • Exomes 𝑓: 0.0057 (95 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA8S NM_001395373.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.53
• Publications: 1 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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0069929957).
• BP6: Variant 15-23360525-C-T is Benign according to our data. Variant chr15-23360525-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2644967.Status of the report is criteria_provided_single_submitter, 1 stars.

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.818C>T	p.Ser273Leu	missense	Exon 10 of 19	NP_001382302.1	H3BPF8
	GOLGA8S	NM_001355465.2		c.140C>T	p.Ser47Leu	missense	Exon 9 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.818C>T	p.Ser273Leu	missense	Exon 10 of 19	ENSP00000455298.2	H3BPF8
	GOLGA8S	ENST00000604046.1	TSL:1	n.1153C>T		non_coding_transcript_exon	Exon 9 of 18

Frequencies

GnomAD3 genomes AF: 0.00463 AC: 685 AN: 147838 Hom.: 26 Cov.: 27

Gnomad AFR AF: 0.00126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00250

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000226

Gnomad FIN AF: 0.00498

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00749

Gnomad OTH AF: 0.00298

GnomAD2 exomes AF: 0.00457 AC: 298 AN: 65178 AF XY: 0.00464

Gnomad AFR exome AF: 0.00120

Gnomad AMR exome AF: 0.00237

Gnomad ASJ exome AF: 0.0136

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00496

Gnomad NFE exome AF: 0.00760

Gnomad OTH exome AF: 0.00809

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00567 AC: 3792 AN: 668622 Hom.: 95 Cov.: 8 AF XY: 0.00563 AC XY: 2030 AN XY: 360646

African (AFR) AF: 0.000822 AC: 15 AN: 18254

American (AMR) AF: 0.00249 AC: 107 AN: 43058

Ashkenazi Jewish (ASJ) AF: 0.00980 AC: 202 AN: 20604

East Asian (EAS) AF: 0.0000828 AC: 3 AN: 36218

South Asian (SAS) AF: 0.000394 AC: 27 AN: 68510

European-Finnish (FIN) AF: 0.00487 AC: 242 AN: 49718

Middle Eastern (MID) AF: 0.00348 AC: 9 AN: 2586

European-Non Finnish (NFE) AF: 0.00759 AC: 3000 AN: 395448

Other (OTH) AF: 0.00546 AC: 187 AN: 34226

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00464 AC: 687 AN: 147958 Hom.: 27 Cov.: 27 AF XY: 0.00447 AC XY: 322 AN XY: 72096

African (AFR) AF: 0.00126 AC: 50 AN: 39840

American (AMR) AF: 0.00250 AC: 37 AN: 14826

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 39 AN: 3388

East Asian (EAS) AF: 0.00 AC: 0 AN: 5066

South Asian (SAS) AF: 0.000226 AC: 1 AN: 4422

European-Finnish (FIN) AF: 0.00498 AC: 52 AN: 10440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00752 AC: 502 AN: 66792

Other (OTH) AF: 0.00294 AC: 6 AN: 2038

Alfa AF: 0.00157 Hom.: 1

ExAC AF: 0.00121 AC: 55

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.97
FATHMM_MKL	Benign	0.0086	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.00083	T
MetaRNN	Benign	0.0070	T
PhyloP100		1.5
PROVEAN	Uncertain	-3.8	D
Sift	Benign	0.12	T
Sift4G	Benign	0.22	T
Vest4		0.17
MVP		0.32
MPC		1.6
GERP RS		-0.15
Varity_R		0.092
gMVP		0.13
Mutation Taster		=89/11	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: rs530525459; hg19: chr15-23605672;