Genetic Variant GPATCH11:p.Met160Leu (chr2-37092193-A-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_174931.4(GPATCH11):c.478A>C(p.Met160Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 1,567,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

GPATCH11
NM_174931.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00900

Publications

1 publications found

Variant links:

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]

GPATCH11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02326271).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174931.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPATCH11	NM_174931.4	MANE Select	c.478A>C	p.Met160Leu	missense	Exon 6 of 9	NP_777591.4	A0A6I8PRS5
GPATCH11	NM_001371856.3		c.502A>C	p.Met168Leu	missense	Exon 6 of 9	NP_001358785.2
GPATCH11	NM_001371858.3		c.478A>C	p.Met160Leu	missense	Exon 6 of 9	NP_001358787.2	A0A6I8PRS5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPATCH11	ENST00000674370.2	MANE Select	c.478A>C	p.Met160Leu	missense	Exon 6 of 9	ENSP00000501347.1	A0A6I8PRS5
GPATCH11	ENST00000281932.6	TSL:1	c.70A>C	p.Met24Leu	missense	Exon 4 of 7	ENSP00000281932.6	A0A6Q8JGY2
GPATCH11	ENST00000964376.1		c.502A>C	p.Met168Leu	missense	Exon 6 of 9	ENSP00000634435.1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151778

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000192

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:

0.0000600

AC:

AN:

216806

AF XY:

0.0000594

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000855

Gnomad EAS exome

AF:

0.000252

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000197

GnomAD4 exome

AF:

0.0000177

AC:

AN:

1415978

Hom.:

Cov.:

AF XY:

0.0000171

AC XY:

AN XY:

703496

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31156

American (AMR)

AF:

0.00

AC:

AN:

34218

Ashkenazi Jewish (ASJ)

AF:

0.000498

AC:

AN:

24106

East Asian (EAS)

AF:

0.000205

AC:

AN:

38984

South Asian (SAS)

AF:

0.00

AC:

AN:

76980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5558

European-Non Finnish (NFE)

AF:

0.00000365

AC:

AN:

1094588

Other (OTH)

AF:

0.0000172

AC:

AN:

58284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

151778

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74134

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41336

American (AMR)

AF:

0.00

AC:

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3466

East Asian (EAS)

AF:

0.000192

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10472

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67960

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000988

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.69

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.56

M_CAP

Benign

0.0022

MetaRNN

Benign

0.023

MetaSVM

Benign

-1.0

PhyloP100

0.0090

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.95

REVEL

Benign

0.042

Sift

Benign

1.0

Sift4G

Benign

0.61

Polyphen

0.0

Vest4

0.13

MVP

0.040

ClinPred

0.011

GERP RS

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.061

gMVP

0.18

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over