rs142169254

Variant names:

• chr2-37092011-G-A
• rs142169254
• NM_174931.4:c.424G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-37092011-G-A
• chr2-37092011-G-C

Variant summary

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

The NM_174931.4(GPATCH11):​c.424G>A​(p.Glu142Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000276 in 1,613,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: GPATCH11 NM_174931.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.67

Genes affected

GPATCH11 (HGNC:26768): (G-patch domain containing 11) Predicted to enable nucleic acid binding activity. Located in kinetochore. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.06857425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPATCH11	NM_174931.4	c.424G>A	p.Glu142Lys	missense_variant	Exon 5 of 9	ENST00000674370.2	NP_777591.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPATCH11	ENST00000674370.2	c.424G>A	p.Glu142Lys	missense_variant	Exon 5 of 9		NM_174931.4	ENSP00000501347.1
GPATCH11	ENST00000281932.6	c.16G>A	p.Glu6Lys	missense_variant	Exon 3 of 7	1		ENSP00000281932.6
GPATCH11	ENST00000473067.1	n.173G>A		non_coding_transcript_exon_variant	Exon 2 of 4	3

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152080 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

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: 0.000426

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000152 AC: 38 AN: 250046 AF XY: 0.000185

Gnomad AFR exome AF: 0.0000634

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000310

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000284 AC: 415 AN: 1460946 Hom.: 0 Cov.: 30 AF XY: 0.000293 AC XY: 213 AN XY: 726792

African (AFR) AF: 0.0000299 AC: 1 AN: 33452

American (AMR) AF: 0.0000224 AC: 1 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.000361 AC: 401 AN: 1111382

Other (OTH) AF: 0.000199 AC: 12 AN: 60334

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152200 Hom.: 0 Cov.: 31 AF XY: 0.000148 AC XY: 11 AN XY: 74404

African (AFR) AF: 0.0000241 AC: 1 AN: 41540

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

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

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68008

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.000290 Hom.: 0

Bravo AF: 0.000170

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.000115 AC: 14

EpiCase AF: 0.000273

EpiControl AF: 0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.412G>A (p.E138K) alteration is located in exon 5 (coding exon 4) of the GPATCH11 gene. This alteration results from a G to A substitution at nucleotide position 412, causing the glutamic acid (E) at amino acid position 138 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-1.0	T
PhyloP100		5.7
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.5	.;D
REVEL	Benign	0.099
Sift	Uncertain	0.014	.;D
Sift4G	Uncertain	0.027	D;D
Polyphen		0.67	.;P
Vest4		0.26
MVP		0.061
ClinPred		0.13	T
GERP RS		3.9
Varity_R		0.030
gMVP		0.46
Mutation Taster		=79/21	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

Publications

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Other links and lift over

dbSNP: rs142169254; hg19: chr2-37319154;