1-217449305-G-C

Variant names:

• chr1-217449305-G-C
• rs144624552
• NM_018040.5:c.1310C>G

Variant summary

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

The NM_018040.5(GPATCH2):​c.1310C>G​(p.Thr437Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. T437M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPATCH2 NM_018040.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 4 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: 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=0.10542011).

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.1310C>G	p.Thr437Arg	missense	Exon 9 of 10	NP_060510.1	Q9NW75-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPATCH2	ENST00000366935.8	TSL:2 MANE Select	c.1310C>G	p.Thr437Arg	missense	Exon 9 of 10	ENSP00000355902.3	Q9NW75-1
	GPATCH2	ENST00000885578.1		c.1301C>G	p.Thr434Arg	missense	Exon 9 of 10	ENSP00000555637.1
	GPATCH2	ENST00000911527.1		c.1199C>G	p.Thr400Arg	missense	Exon 7 of 8	ENSP00000581586.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.0
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.034
Sift	Benign	0.22	T
Sift4G	Benign	0.19	T
Polyphen		0.53	P
Vest4		0.30
MutPred		0.27		Gain of MoRF binding (P = 0.0235)
MVP		0.41
MPC		0.58
ClinPred		0.45	T
GERP RS		1.9
Varity_R		0.070
gMVP		0.49
Mutation Taster		=89/11	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: rs144624552; hg19: chr1-217622647;