Genetic Variant GPATCH3:p.Pro462Pro (chr1-26891202-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7

The NM_022078.3(GPATCH3):c.1386A>G(p.Pro462Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,613,446 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000088 ( 1 hom. )

Consequence

GPATCH3
NM_022078.3 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.513

Variant links:

Genes affected

GPATCH3 (HGNC:25720): (G-patch domain containing 3) Predicted to enable nucleic acid binding activity. Involved in negative regulation of RIG-I signaling pathway; negative regulation of type I interferon production; and positive regulation of transcription, DNA-templated. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

GPATCH3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 1-26891202-T-C is Benign according to our data. Variant chr1-26891202-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3038161.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.513 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPATCH3	NM_022078.3 link	c.1386A>G	p.Pro462Pro	synonymous_variant	Exon 7 of 7	ENST00000361720.10	NP_071361.2	Q96I76

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GPATCH3	ENST00000361720.10 link	c.1386A>G	p.Pro462Pro	synonymous_variant	Exon 7 of 7	1	NM_022078.3	ENSP00000354645.5	Q96I76
GPATCH3	ENST00000445019.5 link	c.181-351A>G		intron_variant	Intron 2 of 2	3		ENSP00000398563.1	H0Y5H5
GPATCH3	ENST00000450844.1 link	c.240A>G	p.Pro80Pro	synonymous_variant	Exon 3 of 3	2		ENSP00000399036.1	Q5JYG5

Frequencies

GnomAD3 genomes

AF:

0.000789

AC:

120

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00268

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000196

AC:

AN:

250382

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

135378

show subpopulations

Gnomad AFR exome

AF:

0.00296

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000876

AC:

128

AN:

1461198

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

726798

show subpopulations

Gnomad4 AFR exome

AF:

0.00344

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000788

AC:

120

AN:

152248

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00267

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000345

Hom.:

Bravo

AF:

0.000990

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GPATCH3-related disorder

Benign:1

May 03, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.1

DANN

Benign

0.83

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over