chr19-33109992-G-C

Variant names:

• chr19-33109992-G-C
• rs201456156
• NM_018025.3:c.1561G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018025.3(GPATCH1):​c.1561G>C​(p.Val521Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V521I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPATCH1 NM_018025.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062353313).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPATCH1	NM_018025.3	c.1561G>C	p.Val521Leu	missense_variant	Exon 11 of 20	ENST00000170564.7	NP_060495.2
GPATCH1	XM_006723255.5	c.1561G>C	p.Val521Leu	missense_variant	Exon 11 of 14		XP_006723318.1
GPATCH1	NR_135270.2	n.1574G>C		non_coding_transcript_exon_variant	Exon 11 of 21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPATCH1	ENST00000170564.7	c.1561G>C	p.Val521Leu	missense_variant	Exon 11 of 20	1	NM_018025.3	ENSP00000170564.1
GPATCH1	ENST00000590062.1	n.116G>C		non_coding_transcript_exon_variant	Exon 1 of 3	2
GPATCH1	ENST00000592165.1	n.*1017G>C		downstream_gene_variant		5		ENSP00000467632.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.015
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.7
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.085
Sift	Benign	0.64	T
Sift4G	Benign	0.35	T
Polyphen		0.0010	B
Vest4		0.12
MutPred		0.28		Loss of methylation at K524 (P = 0.068);
MVP		0.36
MPC		0.13
ClinPred		0.16	T
GERP RS		5.7
Varity_R		0.028
gMVP		0.18
Mutation Taster		=94/6	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: rs201456156; hg19: chr19-33600898;