dbSNP rs1171334745: AFG2B:p.Ala61Pro (chr15-45402610-G-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_024063.3(AFG2B):c.181G>C(p.Ala61Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AFG2B
NM_024063.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.81

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.774

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.181G>C	p.Ala61Pro	missense	Exon 1 of 8	NP_076968.2	Q9BVQ7-1
AFG2B	NM_001323640.2		c.181G>C	p.Ala61Pro	missense	Exon 1 of 5	NP_001310569.1	Q9BVQ7-2
AFG2B	NR_027635.2		n.275G>C		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.181G>C	p.Ala61Pro	missense	Exon 1 of 8	ENSP00000305494.6	Q9BVQ7-1
AFG2B	ENST00000907461.1		c.181G>C	p.Ala61Pro	missense	Exon 1 of 8	ENSP00000577520.1
AFG2B	ENST00000960280.1		c.181G>C	p.Ala61Pro	missense	Exon 1 of 8	ENSP00000630339.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1423130

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

705586

African (AFR)

AF:

0.00

AC:

AN:

32356

American (AMR)

AF:

0.00

AC:

AN:

39814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25414

East Asian (EAS)

AF:

0.00

AC:

AN:

37138

South Asian (SAS)

AF:

0.00

AC:

AN:

82490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45208

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1096050

Other (OTH)

AF:

0.00

AC:

AN:

58980

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

Pathogenic

0.60

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.10

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.89

M_CAP

Pathogenic

0.42

MetaRNN

Pathogenic

0.77

MetaSVM

Uncertain

0.78

MutationAssessor

Uncertain

2.7

PhyloP100

5.8

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.3

REVEL

Pathogenic

0.67

Sift

Uncertain

0.024

Sift4G

Benign

0.072

Polyphen

0.98

Vest4

0.59

MutPred

0.59

Loss of catalytic residue at A61 (P = 0.0069)

MVP

0.89

MPC

2.1

ClinPred

0.99

GERP RS

4.9

PromoterAI

-0.031

Neutral

(source)

Varity_R

0.90

gMVP

0.94

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