19-33090831-C-G

Variant names:

• chr19-33090831-C-G
• NM_018025.3:c.260C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018025.3(GPATCH1):​c.260C>G​(p.Ser87Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPATCH1 NM_018025.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2474842).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPATCH1	NM_018025.3	c.260C>G	p.Ser87Cys	missense_variant	Exon 3 of 20	ENST00000170564.7	NP_060495.2
GPATCH1	XM_006723255.5	c.260C>G	p.Ser87Cys	missense_variant	Exon 3 of 14		XP_006723318.1
GPATCH1	NR_135270.2	n.273C>G		non_coding_transcript_exon_variant	Exon 3 of 21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPATCH1	ENST00000170564.7	c.260C>G	p.Ser87Cys	missense_variant	Exon 3 of 20	1	NM_018025.3	ENSP00000170564.1
GPATCH1	ENST00000592165.1	n.260C>G		non_coding_transcript_exon_variant	Exon 3 of 10	5		ENSP00000467632.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461162 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726958

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.15
Sift	Benign	0.056	T
Sift4G	Benign	0.079	T
Polyphen		0.95	P
Vest4		0.21
MutPred		0.51		Loss of disorder (P = 0.002);
MVP		0.43
MPC		0.45
ClinPred		0.92	D
GERP RS		6.0
Varity_R		0.15
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-33581737;