Genetic Variant NM_174931.4:c.484C>G (chr2-37092199-C-G) – 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.484C>G(p.Leu162Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000141 in 1,560,280 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 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

GPATCH11
NM_174931.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.79

Publications

0 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=0.03488189).

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.484C>G	p.Leu162Val	missense	Exon 6 of 9	NP_777591.4	A0A6I8PRS5
GPATCH11	NM_001371856.3		c.508C>G	p.Leu170Val	missense	Exon 6 of 9	NP_001358785.2
GPATCH11	NM_001371858.3		c.484C>G	p.Leu162Val	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.484C>G	p.Leu162Val	missense	Exon 6 of 9	ENSP00000501347.1	A0A6I8PRS5
GPATCH11	ENST00000281932.6	TSL:1	c.76C>G	p.Leu26Val	missense	Exon 4 of 7	ENSP00000281932.6	A0A6Q8JGY2
GPATCH11	ENST00000964376.1		c.508C>G	p.Leu170Val	missense	Exon 6 of 9	ENSP00000634435.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151448

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000834

AC:

AN:

215704

AF XY:

0.0000853

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000746

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000142

AC:

AN:

1408832

Hom.:

Cov.:

AF XY:

0.0000157

AC XY:

AN XY:

699876

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31010

American (AMR)

AF:

0.000563

AC:

AN:

33724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24028

East Asian (EAS)

AF:

0.0000259

AC:

AN:

38616

South Asian (SAS)

AF:

0.00

AC:

AN:

75532

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51764

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5530

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1090714

Other (OTH)

AF:

0.00

AC:

AN:

57914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.428

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:

0.0000132

AC:

AN:

151448

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73926

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41250

American (AMR)

AF:

0.000132

AC:

AN:

15160

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67892

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.000142

Hom.:

Bravo

AF:

0.0000416

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

-0.48

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.77

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.84

M_CAP

Benign

0.0025

MetaRNN

Benign

0.035

MetaSVM

Benign

-1.1

PhyloP100

1.8

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.41

REVEL

Benign

0.060

Sift

Benign

0.34

Sift4G

Benign

0.66

Polyphen

0.018

Vest4

0.19

MVP

0.072

ClinPred

0.052

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.047

gMVP

0.18

Mutation Taster

=80/20

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