NM_001350920.2:c.1284T>C

Variant names:

• chr15-28387606-T-C
• rs749508373
• NM_001350920.2:c.1284T>C

Variant summary

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

The NM_001350920.2(GOLGA8F):​c.1284T>C​(p.Asp428Asp) 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 0.00072 (0 hom., cov: 19)
  • Exomes 𝑓: 0.0011 (15 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA8F NM_001350920.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.25
• Publications: 0 publications found

Genes affected

GOLGA8F (HGNC:32378): (golgin A8 family member F) 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]

RN7SL238P (HGNC:46254): (RNA, 7SL, cytoplasmic 238, pseudogene)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 15-28387606-T-C is Benign according to our data. Variant chr15-28387606-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3770810.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.25 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350920.2. 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
	GOLGA8F	NM_001350920.2	MANE Select	c.1284T>C	p.Asp428Asp	synonymous	Exon 15 of 19	NP_001337849.2	P0DX52-1
	GOLGA8F	NR_033351.2		n.1681T>C		non_coding_transcript_exon	Exon 14 of 18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA8F	ENST00000526619.7	TSL:1 MANE Select	c.1284T>C	p.Asp428Asp	synonymous	Exon 15 of 19	ENSP00000456138.3	P0DX52-1
	GOLGA8F	ENST00000532622.8	TSL:5	n.1655T>C		non_coding_transcript_exon	Exon 14 of 18
	RN7SL238P	ENST00000613832.1	TSL:6	n.*121T>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.000725 AC: 100 AN: 137964 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000211

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00180

Gnomad SAS AF: 0.00436

Gnomad FIN AF: 0.000191

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000351

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000746 AC: 148 AN: 198386 AF XY: 0.000860

Gnomad AFR exome AF: 0.000921

Gnomad AMR exome AF: 0.000144

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000988

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000177

Gnomad OTH exome AF: 0.000611

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00110 AC: 841 AN: 767918 Hom.: 15 Cov.: 11 AF XY: 0.00134 AC XY: 548 AN XY: 408412

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

African (AFR) AF: 0.00203 AC: 34 AN: 16738

American (AMR) AF: 0.000438 AC: 19 AN: 43388

Ashkenazi Jewish (ASJ) AF: 0.0000942 AC: 2 AN: 21238

East Asian (EAS) AF: 0.00218 AC: 80 AN: 36746

South Asian (SAS) AF: 0.00613 AC: 438 AN: 71396

European-Finnish (FIN) AF: 0.0000753 AC: 4 AN: 53134

Middle Eastern (MID) AF: 0.00118 AC: 4 AN: 3384

European-Non Finnish (NFE) AF: 0.000462 AC: 224 AN: 484644

Other (OTH) AF: 0.000966 AC: 36 AN: 37250

⚠️ 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: 0.000724 AC: 100 AN: 138044 Hom.: 0 Cov.: 19 AF XY: 0.000802 AC XY: 54 AN XY: 67358

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

African (AFR) AF: 0.00137 AC: 44 AN: 32082

American (AMR) AF: 0.000210 AC: 3 AN: 14258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3222

East Asian (EAS) AF: 0.00181 AC: 9 AN: 4976

South Asian (SAS) AF: 0.00436 AC: 19 AN: 4356

European-Finnish (FIN) AF: 0.000191 AC: 2 AN: 10470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.000351 AC: 23 AN: 65608

Other (OTH) AF: 0.00 AC: 0 AN: 1908

⚠️ 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: 0.000675 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
PhyloP100		-1.3
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs749508373; hg19: chr15-28632752;