Genetic Variant GPANK1:p.Arg322Gly (chr6-31662373-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033177.4(GPANK1):c.964A>G(p.Arg322Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,459,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

GPANK1
NM_033177.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64

Publications

0 publications found

Variant links:

Genes affected

GPANK1 (HGNC:13920): (G-patch domain and ankyrin repeats 1) This gene is located in a cluster of HLA-B-associated transcripts, which is included in the human major histocompatability complex III region. This gene encodes a protein which is thought to play a role in immunity. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Nov 2010]

GPANK1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21163067).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033177.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPANK1	NM_033177.4	MANE Select	c.964A>G	p.Arg322Gly	missense	Exon 3 of 3	NP_149417.1	O95872
GPANK1	NM_001199237.1		c.964A>G	p.Arg322Gly	missense	Exon 4 of 4	NP_001186166.1	A0A024RCU2
GPANK1	NM_001199238.1		c.964A>G	p.Arg322Gly	missense	Exon 4 of 4	NP_001186167.1	A0A024RCU2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPANK1	ENST00000375896.9	TSL:1 MANE Select	c.964A>G	p.Arg322Gly	missense	Exon 3 of 3	ENSP00000365060.4	O95872
GPANK1	ENST00000375893.6	TSL:5	c.964A>G	p.Arg322Gly	missense	Exon 4 of 4	ENSP00000365057.2	O95872
GPANK1	ENST00000375895.6	TSL:5	c.964A>G	p.Arg322Gly	missense	Exon 4 of 4	ENSP00000365059.2	O95872

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000406

AC:

AN:

246036

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000905

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1459964

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726304

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26096

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52304

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000810

AC:

AN:

1111536

Other (OTH)

AF:

0.00

AC:

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000848

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

0.13

BayesDel_addAF

Uncertain

0.043

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.79

M_CAP

Benign

0.0085

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.7

PhyloP100

1.6

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.18

Sift

Uncertain

0.020

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.33

MutPred

0.24

Loss of MoRF binding (P = 0.0262)

MVP

0.39

MPC

0.96

ClinPred

0.94

GERP RS

3.8

Varity_R

0.48

gMVP

0.73

Mutation Taster

=67/33

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over