Genetic Variant GPATCH1:p.Val77Ala (chr19-33090801-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_018025.3(GPATCH1):c.230T>C(p.Val77Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,038 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

GPATCH1
NM_018025.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.39

Publications

2 publications found

Variant links:

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]

GPATCH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPATCH1	NM_018025.3 link	c.230T>C	p.Val77Ala	missense_variant	Exon 3 of 20	ENST00000170564.7	NP_060495.2	Q9BRR8
GPATCH1	XM_006723255.5 link	c.230T>C	p.Val77Ala	missense_variant	Exon 3 of 14		XP_006723318.1
GPATCH1	NR_135270.2 link	n.243T>C		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 link	c.230T>C	p.Val77Ala	missense_variant	Exon 3 of 20	1	NM_018025.3	ENSP00000170564.1		Q9BRR8
GPATCH1	ENST00000592165.1 link	n.230T>C		non_coding_transcript_exon_variant	Exon 3 of 10	5		ENSP00000467632.1		K7EQ19

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460038

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726482

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33444

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53350

Middle Eastern (MID)

AF:

0.000521

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110424

Other (OTH)

AF:

0.0000166

AC:

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 27, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.230T>C (p.V77A) alteration is located in exon 3 (coding exon 3) of the GPATCH1 gene. This alteration results from a T to C substitution at nucleotide position 230, causing the valine (V) at amino acid position 77 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.0058

MetaRNN

Uncertain

0.49

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

2.9

PhyloP100

7.4

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.77

REVEL

Benign

0.12

Sift

Benign

0.12

Sift4G

Benign

0.13

Polyphen

0.59

Vest4

0.47

MutPred

0.44

Loss of sheet (P = 0.0181);

MVP

0.33

MPC

0.27

ClinPred

0.53

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.077

gMVP

0.37

Mutation Taster

=52/48

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr19-33090801-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over