chr15-32446531-C-T

Variant names:

• chr15-32446531-C-T
• rs772846509
• NM_001277308.1:c.1311G>A

Variant summary

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

The NM_001277308.1(GOLGA8O):​c.1311G>A​(p.Glu437Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00042 (0 hom., cov: 19)
  • Exomes 𝑓: 0.00029 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA8O NM_001277308.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.354
• Publications: 0 publications found

Genes affected

GOLGA8O (HGNC:44406): (golgin A8 family member O) Predicted to be involved in Golgi organization. Predicted to be located in Golgi apparatus. Predicted to be active in Golgi cis cisterna; Golgi cisterna membrane; and cis-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

RN7SL539P (HGNC:46555): (RNA, 7SL, cytoplasmic 539, pseudogene)

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 15-32446531-C-T is Benign according to our data. Variant chr15-32446531-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2645125.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.354 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277308.1. 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
	GOLGA8O	NM_001277308.1	MANE Select	c.1311G>A	p.Glu437Glu	synonymous	Exon 15 of 19	NP_001264237.1	A6NCC3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA8O	ENST00000509311.7	TSL:5 MANE Select	c.1311G>A	p.Glu437Glu	synonymous	Exon 15 of 19	ENSP00000423159.2	A6NCC3-2
	RN7SL539P	ENST00000610974.1	TSL:6	n.*143G>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.000416 AC: 54 AN: 129798 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.0000843

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000417

Gnomad ASJ AF: 0.00255

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000590

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000540

Gnomad OTH AF: 0.00171

GnomAD2 exomes AF: 0.00143 AC: 275 AN: 192752 AF XY: 0.00166

Gnomad AFR exome AF: 0.000320

Gnomad AMR exome AF: 0.000762

Gnomad ASJ exome AF: 0.00490

Gnomad EAS exome AF: 0.0000698

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00111

Gnomad OTH exome AF: 0.00239

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000292 AC: 422 AN: 1446992 Hom.: 0 Cov.: 33 AF XY: 0.000363 AC XY: 261 AN XY: 719596

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

African (AFR) AF: 0.0000601 AC: 2 AN: 33272

American (AMR) AF: 0.000320 AC: 14 AN: 43740

Ashkenazi Jewish (ASJ) AF: 0.000703 AC: 18 AN: 25600

East Asian (EAS) AF: 0.00 AC: 0 AN: 37530

South Asian (SAS) AF: 0.00116 AC: 98 AN: 84738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52906

Middle Eastern (MID) AF: 0.00167 AC: 8 AN: 4802

European-Non Finnish (NFE) AF: 0.000232 AC: 256 AN: 1104872

Other (OTH) AF: 0.000437 AC: 26 AN: 59532

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.000416 AC: 54 AN: 129914 Hom.: 0 Cov.: 19 AF XY: 0.000428 AC XY: 27 AN XY: 63104

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

African (AFR) AF: 0.0000841 AC: 3 AN: 35692

American (AMR) AF: 0.000417 AC: 5 AN: 11998

Ashkenazi Jewish (ASJ) AF: 0.00255 AC: 8 AN: 3136

East Asian (EAS) AF: 0.00 AC: 0 AN: 2764

South Asian (SAS) AF: 0.000592 AC: 2 AN: 3380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 230

European-Non Finnish (NFE) AF: 0.000540 AC: 33 AN: 61124

Other (OTH) AF: 0.00169 AC: 3 AN: 1772

⚠️ 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: 0.00182 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	-0.69
CADD	Benign	5.4
DANN	Benign	0.72
PhyloP100		-0.35
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: rs772846509; hg19: chr15-32738732; COSMIC: COSV68600960; COSMIC: COSV68600960;