Genetic Variant AFG2B:p.Ala83Thr (chr15-45402676-G-A) – 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_024063.3(AFG2B):c.247G>A(p.Ala83Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

AFG2B
NM_024063.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.541

Publications

0 publications found

Variant links:

Genes affected

AFG2B (HGNC:28762): (AFG2 AAA ATPase homolog B) Predicted to enable ATP binding activity. Located in cytoplasm and spindle. [provided by Alliance of Genome Resources, Apr 2022]

AFG2B Gene-Disease associations (from GenCC):

hearing loss, autosomal recessive 119
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen
neurodevelopmental disorder with hearing loss and spasticity
Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, G2P

AFG2B links:

Genome browser will be placed here

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=0.085867256).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024063.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AFG2B	NM_024063.3	MANE Select	c.247G>A	p.Ala83Thr	missense	Exon 1 of 8	NP_076968.2	Q9BVQ7-1
AFG2B	NM_001323640.2		c.247G>A	p.Ala83Thr	missense	Exon 1 of 5	NP_001310569.1	Q9BVQ7-2
AFG2B	NR_027635.2		n.341G>A		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AFG2B	ENST00000305560.11	TSL:1 MANE Select	c.247G>A	p.Ala83Thr	missense	Exon 1 of 8	ENSP00000305494.6	Q9BVQ7-1
AFG2B	ENST00000907461.1		c.247G>A	p.Ala83Thr	missense	Exon 1 of 8	ENSP00000577520.1
AFG2B	ENST00000960280.1		c.247G>A	p.Ala83Thr	missense	Exon 1 of 8	ENSP00000630339.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000552

AC:

AN:

181308

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:

0.0000129

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.02e-7

AC:

AN:

1424210

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706566

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32270

American (AMR)

AF:

0.00

AC:

AN:

41486

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25426

East Asian (EAS)

AF:

0.00

AC:

AN:

37804

South Asian (SAS)

AF:

0.00

AC:

AN:

82418

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41344

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5300

European-Non Finnish (NFE)

AF:

9.10e-7

AC:

AN:

1099084

Other (OTH)

AF:

0.00

AC:

AN:

59078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Benign

8.2

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0072

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.56

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.086

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.3

PhyloP100

-0.54

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.59

REVEL

Benign

0.17

Sift

Benign

0.40

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.029

MutPred

0.21

Gain of sheet (P = 0.0125)

MVP

0.61

MPC

0.92

ClinPred

0.055

GERP RS

-2.9

PromoterAI

0.0050

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.050

gMVP

0.54

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over