chr1-217610353-T-C

Variant names:

• chr1-217610353-T-C
• rs369527117
• NM_018040.5:c.1066A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018040.5(GPATCH2):​c.1066A>G​(p.Ile356Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 1,604,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: GPATCH2 NM_018040.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06990367).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018040.5. 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
	GPATCH2	NM_018040.5	MANE Select	c.1066A>G	p.Ile356Val	missense	Exon 5 of 10	NP_060510.1	Q9NW75-1
	GPATCH2	NM_001297754.3		c.1066A>G	p.Ile356Val	missense	Exon 5 of 6	NP_001284683.1	Q9NW75-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPATCH2	ENST00000366935.8	TSL:2 MANE Select	c.1066A>G	p.Ile356Val	missense	Exon 5 of 10	ENSP00000355902.3	Q9NW75-1
	GPATCH2	ENST00000366934.3	TSL:1	c.1066A>G	p.Ile356Val	missense	Exon 5 of 6	ENSP00000355901.3	Q9NW75-2
	GPATCH2	ENST00000885578.1		c.1057A>G	p.Ile353Val	missense	Exon 5 of 10	ENSP00000555637.1

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000280 AC: 7 AN: 250080 AF XY: 0.0000370

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000689 AC: 10 AN: 1452212 Hom.: 0 Cov.: 27 AF XY: 0.00000968 AC XY: 7 AN XY: 723000

African (AFR) AF: 0.000120 AC: 4 AN: 33244

American (AMR) AF: 0.0000673 AC: 3 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103876

Other (OTH) AF: 0.0000333 AC: 2 AN: 60058

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74492

African (AFR) AF: 0.000433 AC: 18 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000161 Hom.: 0

Bravo AF: 0.000117

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.075
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.1
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.074
Sift	Benign	0.18	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.16
MVP		0.42
MPC		0.31
ClinPred		0.010	T
GERP RS		2.6
Varity_R		0.048
gMVP		0.20
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs369527117; hg19: chr1-217783695;