rs762171565

Variant names:

• chr15-23365041-G-A
• rs762171565
• NM_001395373.1:c.1824G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001395373.1(GOLGA8S):​c.1824G>A​(p.Pro608Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 144,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 21)
  • Exomes 𝑓: 0.00031 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA8S NM_001395373.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.252
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 15-23365041-G-A is Benign according to our data. Variant chr15-23365041-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2644970.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.252 with no splicing effect.

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.1824G>A	p.Pro608Pro	synonymous	Exon 19 of 19	NP_001382302.1	H3BPF8
	GOLGA8S	NM_001355465.2		c.1146G>A	p.Pro382Pro	synonymous	Exon 18 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.1824G>A	p.Pro608Pro	synonymous	Exon 19 of 19	ENSP00000455298.2	H3BPF8
	GOLGA8S	ENST00000604046.1	TSL:1	n.2159G>A		non_coding_transcript_exon	Exon 18 of 18

Frequencies

GnomAD3 genomes AF: 0.000159 AC: 23 AN: 144508 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.0000264

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: 0.000197

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000303

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000220 AC: 50 AN: 227190 AF XY: 0.000264

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000162

Gnomad NFE exome AF: 0.000415

Gnomad OTH exome AF: 0.000175

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000306 AC: 440 AN: 1435654 Hom.: 4 Cov.: 36 AF XY: 0.000287 AC XY: 205 AN XY: 714784

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32612

American (AMR) AF: 0.0000224 AC: 1 AN: 44552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.0000938 AC: 8 AN: 85296

European-Finnish (FIN) AF: 0.000254 AC: 11 AN: 43252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4120

European-Non Finnish (NFE) AF: 0.000370 AC: 407 AN: 1100564

Other (OTH) AF: 0.000202 AC: 12 AN: 59542

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000159 AC: 23 AN: 144508 Hom.: 0 Cov.: 21 AF XY: 0.000185 AC XY: 13 AN XY: 70372

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000264 AC: 1 AN: 37846

American (AMR) AF: 0.00 AC: 0 AN: 14438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3414

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4382

European-Finnish (FIN) AF: 0.000197 AC: 2 AN: 10178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.000303 AC: 20 AN: 66030

Other (OTH) AF: 0.00 AC: 0 AN: 1928

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000169 Hom.: 0

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
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.22
DANN	Benign	0.75
PhyloP100		-0.25
Mutation Taster		=100/0	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: rs762171565; hg19: chr15-23610188;