rs2287679

Variant names:

• chr19-33109858-T-C
• rs2287679
• NM_018025.3:c.1427T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-33109858-T-C
• chr19-33109858-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018025.3(GPATCH1):​c.1427T>C​(p.Leu476Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,613,746 control chromosomes in the GnomAD database, including 92,389 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. L476F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.41 (16536 hom., cov: 32)
  • Exomes 𝑓: 0.30 (75853 hom.)
• Consequence: GPATCH1 NM_018025.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 48 publications found

Genes affected

GPATCH1 (HGNC:24658): (G-patch domain containing 1) Predicted to enable RNA binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Part of catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.7734677E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018025.3. 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
	GPATCH1	NM_018025.3	MANE Select	c.1427T>C	p.Leu476Pro	missense	Exon 11 of 20	NP_060495.2
	GPATCH1	NR_135270.2		n.1440T>C		non_coding_transcript_exon	Exon 11 of 21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPATCH1	ENST00000170564.7	TSL:1 MANE Select	c.1427T>C	p.Leu476Pro	missense	Exon 11 of 20	ENSP00000170564.1	Q9BRR8
	GPATCH1	ENST00000939189.1		c.1493T>C	p.Leu498Pro	missense	Exon 12 of 21	ENSP00000609248.1
	GPATCH1	ENST00000880979.1		c.1427T>C	p.Leu476Pro	missense	Exon 11 of 19	ENSP00000551038.1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62983 AN: 151984 Hom.: 16496 Cov.: 32

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.377

GnomAD2 exomes AF: 0.358 AC: 89655 AN: 250630 AF XY: 0.364

Gnomad AFR exome AF: 0.740

Gnomad AMR exome AF: 0.282

Gnomad ASJ exome AF: 0.317

Gnomad EAS exome AF: 0.514

Gnomad FIN exome AF: 0.250

Gnomad NFE exome AF: 0.259

Gnomad OTH exome AF: 0.324

GnomAD4 exome AF: 0.298 AC: 436233 AN: 1461644 Hom.: 75853 Cov.: 35 AF XY: 0.307 AC XY: 223339 AN XY: 727126

African (AFR) AF: 0.751 AC: 25141 AN: 33478

American (AMR) AF: 0.287 AC: 12846 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 8211 AN: 26134

East Asian (EAS) AF: 0.481 AC: 19111 AN: 39694

South Asian (SAS) AF: 0.604 AC: 52122 AN: 86244

European-Finnish (FIN) AF: 0.248 AC: 13248 AN: 53374

Middle Eastern (MID) AF: 0.479 AC: 2762 AN: 5766

European-Non Finnish (NFE) AF: 0.254 AC: 281934 AN: 1111854

Other (OTH) AF: 0.345 AC: 20858 AN: 60382

GnomAD4 genome AF: 0.415 AC: 63077 AN: 152102 Hom.: 16536 Cov.: 32 AF XY: 0.418 AC XY: 31060 AN XY: 74348

African (AFR) AF: 0.728 AC: 30217 AN: 41498

American (AMR) AF: 0.324 AC: 4956 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1119 AN: 3470

East Asian (EAS) AF: 0.500 AC: 2583 AN: 5170

South Asian (SAS) AF: 0.619 AC: 2979 AN: 4816

European-Finnish (FIN) AF: 0.246 AC: 2602 AN: 10572

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17435 AN: 67980

Other (OTH) AF: 0.380 AC: 802 AN: 2108

Alfa AF: 0.316 Hom.: 26179

Bravo AF: 0.432

TwinsUK AF: 0.249 AC: 923

ALSPAC AF: 0.250 AC: 963

ESP6500AA AF: 0.727 AC: 3203

ESP6500EA AF: 0.267 AC: 2297

ExAC AF: 0.370 AC: 44902

Asia WGS AF: 0.588 AC: 2041 AN: 3478

EpiCase AF: 0.274

EpiControl AF: 0.271

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.041
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.61
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.0000018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N
PhyloP100		1.1
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.11
Sift	Benign	0.36	T
Sift4G	Benign	0.25	T
Polyphen		0.0	B
Vest4		0.016
MPC		0.21
ClinPred		0.0011	T
GERP RS		5.7
Varity_R		0.051
gMVP		0.25
Mutation Taster		=96/4	polymorphism (auto)

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: rs2287679; hg19: chr19-33600764; COSMIC: COSV50111027; COSMIC: COSV50111027;