5-32126613-A-G

Variant names:

• chr5-32126613-A-G
• rs61751182
• NM_022130.4:c.496T>C

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.496T>C​(p.Leu166Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,612,862 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0034 (18 hom.)
• Consequence: GOLPH3 NM_022130.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.67
• 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=-0.53).
• BP6: Variant 5-32126613-A-G is Benign according to our data. Variant chr5-32126613-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2655385.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.67 with no splicing effect.
• BS2: High AC in GnomAd4 at 397 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLPH3	NM_022130.4	c.496T>C	p.Leu166Leu	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.496T>C	p.Leu166Leu	synonymous_variant	Exon 4 of 4	1	NM_022130.4	ENSP00000265070.6
GOLPH3	ENST00000503610.5	n.*278T>C		non_coding_transcript_exon_variant	Exon 4 of 4	3		ENSP00000426752.1
GOLPH3	ENST00000512668.1	n.647T>C		non_coding_transcript_exon_variant	Exon 3 of 3	3
GOLPH3	ENST00000503610.5	n.*278T>C		3_prime_UTR_variant	Exon 4 of 4	3		ENSP00000426752.1

Frequencies

GnomAD3 genomes AF: 0.00261 AC: 397 AN: 152214 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00294

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00406

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00269 AC: 675 AN: 250520 AF XY: 0.00262

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00314

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00519

Gnomad NFE exome AF: 0.00380

Gnomad OTH exome AF: 0.00262

GnomAD4 exome AF: 0.00345 AC: 5038 AN: 1460530 Hom.: 18 Cov.: 30 AF XY: 0.00338 AC XY: 2453 AN XY: 726542

African (AFR) AF: 0.000510 AC: 17 AN: 33350

American (AMR) AF: 0.00361 AC: 161 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86096

European-Finnish (FIN) AF: 0.00513 AC: 274 AN: 53392

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5760

European-Non Finnish (NFE) AF: 0.00393 AC: 4362 AN: 1111272

Other (OTH) AF: 0.00338 AC: 204 AN: 60320

GnomAD4 genome AF: 0.00261 AC: 397 AN: 152332 Hom.: 2 Cov.: 33 AF XY: 0.00256 AC XY: 191 AN XY: 74488

African (AFR) AF: 0.000650 AC: 27 AN: 41568

American (AMR) AF: 0.00294 AC: 45 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00377 AC: 40 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00406 AC: 276 AN: 68032

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00290 Hom.: 0

Bravo AF: 0.00260

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00382

EpiControl AF: 0.00373

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	-0.53
CADD	Benign	3.3
DANN	Benign	0.67
PhyloP100		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs61751182; hg19: chr5-32126719; COSMIC: COSV99417580; COSMIC: COSV99417580;