Genetic Variant GPATCH2:p.Asn468Ser (chr1-217431329-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018040.5(GPATCH2):c.1403A>G(p.Asn468Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,454,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

GPATCH2
NM_018040.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.448

Variant links:

Genes affected

GPATCH2 (HGNC:25499): (G-patch domain containing 2) The gene encodes a nuclear factor that may play a role in spermatogenesis and in tumor growth during breast cancer. The encoded protein contains a G-patch domain with an RNA binding motif. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

GPATCH2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03174001).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
GPATCH2	NM_018040.5 link	c.1403A>G	p.Asn468Ser	missense_variant	Exon 10 of 10	ENST00000366935.8	NP_060510.1
GPATCH2	XM_011509689.4 link	c.1472A>G	p.Asn491Ser	missense_variant	Exon 11 of 11		XP_011507991.1
GPATCH2	XM_011509690.4 link	c.1361A>G	p.Asn454Ser	missense_variant	Exon 9 of 9		XP_011507992.1
GPATCH2	XM_017001592.3 link	c.1292A>G	p.Asn431Ser	missense_variant	Exon 8 of 8		XP_016857081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPATCH2	ENST00000366935.8 link	c.1403A>G	p.Asn468Ser	missense_variant	Exon 10 of 10	2	NM_018040.5	ENSP00000355902.3		Q9NW75-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250258

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135364

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1454902

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724346

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1403A>G (p.N468S) alteration is located in exon 10 (coding exon 10) of the GPATCH2 gene. This alteration results from a A to G substitution at nucleotide position 1403, causing the asparagine (N) at amino acid position 468 to be replaced by a serine (S). 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

0.072

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.4

DANN

Benign

0.94

DEOGEN2

Benign

0.00078

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.63

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0037

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.83

PrimateAI

Benign

0.41

PROVEAN

Benign

0.14

REVEL

Benign

0.028

Sift

Benign

0.81

Sift4G

Benign

0.85

Polyphen

0.0010

Vest4

0.090

MutPred

0.32

Gain of MoRF binding (P = 0.1737);

MVP

0.15

MPC

0.29

ClinPred

0.050

GERP RS

-0.40

Varity_R

0.036

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over