19-33108221-T-C

Variant names:

• chr19-33108221-T-C
• rs10416218
• NM_018025.3:c.1285+1322T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018025.3(GPATCH1):​c.1285+1322T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,816 control chromosomes in the GnomAD database, including 16,429 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (16429 hom., cov: 31)
• Consequence: GPATCH1 NM_018025.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.576
• Publications: 36 publications found

Genes affected

GPATCH1 (HGNC:24658): (G-patch domain containing 1) Predicted to enable RNA binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Part of catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018025.3. 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
	GPATCH1	NM_018025.3	MANE Select	c.1285+1322T>C		intron	N/A	NP_060495.2
	GPATCH1	NR_135270.2		n.1298+1322T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPATCH1	ENST00000170564.7	TSL:1 MANE Select	c.1285+1322T>C		intron	N/A	ENSP00000170564.1
	GPATCH1	ENST00000939189.1		c.1351+1322T>C		intron	N/A	ENSP00000609248.1
	GPATCH1	ENST00000880979.1		c.1285+1322T>C		intron	N/A	ENSP00000551038.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62700 AN: 151698 Hom.: 16391 Cov.: 31

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.376

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.414 AC: 62793 AN: 151816 Hom.: 16429 Cov.: 31 AF XY: 0.417 AC XY: 30914 AN XY: 74212

African (AFR) AF: 0.728 AC: 30157 AN: 41412

American (AMR) AF: 0.323 AC: 4924 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1116 AN: 3468

East Asian (EAS) AF: 0.476 AC: 2441 AN: 5128

South Asian (SAS) AF: 0.618 AC: 2976 AN: 4814

European-Finnish (FIN) AF: 0.246 AC: 2595 AN: 10564

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.256 AC: 17400 AN: 67880

Other (OTH) AF: 0.379 AC: 800 AN: 2112

Alfa AF: 0.309 Hom.: 23755

Bravo AF: 0.430

Asia WGS AF: 0.585 AC: 2030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.49
DANN	Benign	0.35
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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: rs10416218; hg19: chr19-33599127;