5-32126368-G-A

Variant names:

• chr5-32126368-G-A
• rs61748192
• NM_022130.4:c.741C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_022130.4(GOLPH3):​c.741C>T​(p.Asp247Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 1,614,142 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (14 hom.)
• Consequence: GOLPH3 NM_022130.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.517
• Publications: 1 publications found

Genes affected

GOLPH3 (HGNC:15452): (golgi phosphoprotein 3) The Golgi complex plays a key role in the sorting and modification of proteins exported from the endoplasmic reticulum. The protein encoded by this gene is a peripheral membrane protein of the Golgi stack and may have a regulatory role in Golgi trafficking. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of these variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 5-32126368-G-A is Benign according to our data. Variant chr5-32126368-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2655384.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.517 with no splicing effect.
• BS2: High AC in GnomAd4 at 464 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLPH3	NM_022130.4	c.741C>T	p.Asp247Asp	synonymous_variant	Exon 4 of 4	ENST00000265070.7	NP_071413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLPH3	ENST00000265070.7	c.741C>T	p.Asp247Asp	synonymous_variant	Exon 4 of 4	1	NM_022130.4	ENSP00000265070.6
GOLPH3	ENST00000503610.5	n.*523C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 4	3		ENSP00000426752.1
GOLPH3	ENST00000503610.5	n.*523C>T		3_prime_UTR_variant	Exon 4 of 4	3		ENSP00000426752.1
GOLPH3	ENST00000512668.1	n.*227C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.00304 AC: 463 AN: 152142 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00447

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00299 AC: 753 AN: 251428 AF XY: 0.00307

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.0170

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00134

Gnomad NFE exome AF: 0.00413

Gnomad OTH exome AF: 0.00456

GnomAD4 exome AF: 0.00383 AC: 5594 AN: 1461882 Hom.: 14 Cov.: 31 AF XY: 0.00381 AC XY: 2771 AN XY: 727240

African (AFR) AF: 0.000568 AC: 19 AN: 33480

American (AMR) AF: 0.00145 AC: 65 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 451 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86258

European-Finnish (FIN) AF: 0.00168 AC: 90 AN: 53420

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00422 AC: 4689 AN: 1112002

Other (OTH) AF: 0.00444 AC: 268 AN: 60394

GnomAD4 genome AF: 0.00305 AC: 464 AN: 152260 Hom.: 3 Cov.: 32 AF XY: 0.00273 AC XY: 203 AN XY: 74456

African (AFR) AF: 0.000554 AC: 23 AN: 41544

American (AMR) AF: 0.00477 AC: 73 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00447 AC: 304 AN: 68024

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00457 Hom.: 1

Bravo AF: 0.00347

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00393

EpiControl AF: 0.00468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GOLPH3: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.4
DANN	Benign	0.77
PhyloP100		0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=90/10	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: rs61748192; hg19: chr5-32126474;