19-33109858-T-G

Variant names:

• chr19-33109858-T-G
• rs2287679
• NM_018025.3:c.1427T>G

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.1427T>G​(p.Leu476Arg) 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. L476F) 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: 1.07
• Publications: 48 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=0.043560594).

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.1427T>G	p.Leu476Arg	missense	Exon 11 of 20	NP_060495.2
	GPATCH1	NR_135270.2		n.1440T>G		non_coding_transcript_exon	Exon 11 of 21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPATCH1	ENST00000170564.7	TSL:1 MANE Select	c.1427T>G	p.Leu476Arg	missense	Exon 11 of 20	ENSP00000170564.1	Q9BRR8
	GPATCH1	ENST00000939189.1		c.1493T>G	p.Leu498Arg	missense	Exon 12 of 21	ENSP00000609248.1
	GPATCH1	ENST00000880979.1		c.1427T>G	p.Leu476Arg	missense	Exon 11 of 19	ENSP00000551038.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.35
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.1
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.088
Sift	Benign	0.59	T
Sift4G	Benign	0.29	T
Polyphen		0.12	B
Vest4		0.078
MutPred		0.35		Gain of solvent accessibility (P = 1e-04)
MVP		0.22
MPC		0.24
ClinPred		0.054	T
GERP RS		5.7
Varity_R		0.069
gMVP		0.32
Mutation Taster		=97/3	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: rs2287679; hg19: chr19-33600764;