1-217431329-T-C

Position:

• chr1-217431329-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448

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]

ACMG classification

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/exons	MANE	UniProt
GPATCH2	NM_018040.5	c.1403A>G	p.Asn468Ser	missense_variant	10/10	ENST00000366935.8
GPATCH2	XM_011509689.4	c.1472A>G	p.Asn491Ser	missense_variant	11/11
GPATCH2	XM_011509690.4	c.1361A>G	p.Asn454Ser	missense_variant	9/9
GPATCH2	XM_017001592.3	c.1292A>G	p.Asn431Ser	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPATCH2	ENST00000366935.8	c.1403A>G	p.Asn468Ser	missense_variant	10/10	2	NM_018040.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 250258 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135364

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: 5 AN: 1454902 Hom.: 0 Cov.: 27 AF XY: 0.00000276 AC XY: 2 AN XY: 724346

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.: 33

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.4
DANN	Benign	0.94
DEOGEN2	Benign	0.00078	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.83	N
MutationTaster	Benign	0.99	N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.028
Sift	Benign	0.81	T
Sift4G	Benign	0.85	T
Polyphen		0.0010	B
Vest4		0.090
MutPred		0.32		Gain of MoRF binding (P = 0.1737);
MVP		0.15
MPC		0.29
ClinPred		0.050	T
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

Other links and lift over

dbSNP: rs776964736; hg19: chr1-217604671; COSMIC: COSV105918144;