1-26891208-T-C

Variant names:

• chr1-26891208-T-C
• rs35647061
• NM_022078.3:c.1380A>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_022078.3(GPATCH3):​c.1380A>G​(p.Leu460Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,613,314 control chromosomes in the GnomAD database, including 7 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 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (7 hom.)
• Consequence: GPATCH3 NM_022078.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.11

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 1-26891208-T-C is Benign according to our data. Variant chr1-26891208-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3044306.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.11 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPATCH3	NM_022078.3	c.1380A>G	p.Leu460Leu	synonymous_variant	Exon 7 of 7	ENST00000361720.10	NP_071361.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPATCH3	ENST00000361720.10	c.1380A>G	p.Leu460Leu	synonymous_variant	Exon 7 of 7	1	NM_022078.3	ENSP00000354645.5
GPATCH3	ENST00000445019.5	c.181-357A>G		intron_variant	Intron 2 of 2	3		ENSP00000398563.1
GPATCH3	ENST00000450844.1	c.234A>G	p.Leu78Leu	synonymous_variant	Exon 3 of 3	2		ENSP00000399036.1

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 199 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00234

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00134 AC: 334 AN: 250070 Hom.: 2 AF XY: 0.00135 AC XY: 183 AN XY: 135246

Gnomad AFR exome AF: 0.000494

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00193

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.00183

Gnomad OTH exome AF: 0.00344

GnomAD4 exome AF: 0.00271 AC: 3961 AN: 1461020 Hom.: 7 Cov.: 31 AF XY: 0.00268 AC XY: 1945 AN XY: 726706

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.00119

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00190

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.00318

Gnomad4 OTH exome AF: 0.00315

GnomAD4 genome AF: 0.00131 AC: 199 AN: 152294 Hom.: 0 Cov.: 32 AF XY: 0.00101 AC XY: 75 AN XY: 74468

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00234

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00194 Hom.: 0

Bravo AF: 0.00144

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00202

EpiControl AF: 0.00202

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

GPATCH3-related disorder Benign:1

Mar 28, 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	-0.71
CADD	Benign	0.96
DANN	Benign	0.69

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

Other links and lift over

dbSNP: rs35647061; hg19: chr1-27217699;