chr1-217431302-T-C

Variant names:

• chr1-217431302-T-C
• rs756842146
• NM_018040.5:c.1430A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_018040.5(GPATCH2):​c.1430A>G​(p.Asn477Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,609,466 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: GPATCH2 NM_018040.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.672
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0441615).
• BP6: Variant 1-217431302-T-C is Benign according to our data. Variant chr1-217431302-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2545562.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1430A>G	p.Asn477Ser	missense	Exon 10 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.1430A>G	p.Asn477Ser	missense	Exon 10 of 10	ENSP00000355902.3	Q9NW75-1
	GPATCH2	ENST00000885578.1		c.1421A>G	p.Asn474Ser	missense	Exon 10 of 10	ENSP00000555637.1
	GPATCH2	ENST00000911527.1		c.1319A>G	p.Asn440Ser	missense	Exon 8 of 8	ENSP00000581586.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251120 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000480 AC: 7 AN: 1457240 Hom.: 0 Cov.: 27 AF XY: 0.00000689 AC XY: 5 AN XY: 725346

African (AFR) AF: 0.00 AC: 0 AN: 33378

American (AMR) AF: 0.0000671 AC: 3 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1107790

Other (OTH) AF: 0.00 AC: 0 AN: 60248

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.059
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.1
DANN	Benign	0.81
DEOGEN2	Benign	0.00083	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.27	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.67
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.82	N
REVEL	Benign	0.047
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.098
MutPred		0.39		Loss of MoRF binding (P = 0.1351)
MVP		0.26
MPC		0.29
ClinPred		0.025	T
GERP RS		3.5
Varity_R		0.051
gMVP		0.15
Mutation Taster		=95/5	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: rs756842146; hg19: chr1-217604644;