NM_018025.3:c.446C>A

Variant names:

• chr19-33093510-C-A
• rs146466271
• NM_018025.3:c.446C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018025.3(GPATCH1):​c.446C>A​(p.Thr149Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. T149M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GPATCH1 NM_018025.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.16
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16841063).

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.446C>A	p.Thr149Lys	missense	Exon 4 of 20	NP_060495.2
	GPATCH1	NR_135270.2		n.459C>A		non_coding_transcript_exon	Exon 4 of 21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPATCH1	ENST00000170564.7	TSL:1 MANE Select	c.446C>A	p.Thr149Lys	missense	Exon 4 of 20	ENSP00000170564.1	Q9BRR8
	GPATCH1	ENST00000939189.1		c.446C>A	p.Thr149Lys	missense	Exon 4 of 21	ENSP00000609248.1
	GPATCH1	ENST00000880979.1		c.446C>A	p.Thr149Lys	missense	Exon 4 of 19	ENSP00000551038.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459424 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725954

African (AFR) AF: 0.00 AC: 0 AN: 33368

American (AMR) AF: 0.00 AC: 0 AN: 44014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26010

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 85824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111056

Other (OTH) AF: 0.00 AC: 0 AN: 60302

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Benign	0.75
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		5.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.070
Sift	Benign	0.86	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.29
MutPred		0.40		Loss of phosphorylation at T149 (P = 0.0324)
MVP		0.32
MPC		0.16
ClinPred		0.57	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.52
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs146466271; hg19: chr19-33584416;