Variant 2-68157322-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138458.4(DNAAF10):c.122G>A(p.Arg41Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

DNAAF10
NM_138458.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.25

Variant links:

Genes affected

DNAAF10 (HGNC:25176): (dynein axonemal assembly factor 10) This gene encodes a protein with two WD40 repeat domains thought to be involved in an apoptosis via activation of caspase-3. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

DNAAF10 links:

ENSG00000273398 (HGNC:):

ENSG00000273398 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF10	NM_138458.4 linkuse as main transcript	c.122G>A	p.Arg41Gln	missense_variant	1/8	ENST00000295121.11	NP_612467.1	Q96MX6-1A0A140VK67
DNAAF10	NM_001256476.2 linkuse as main transcript	c.122G>A	p.Arg41Gln	missense_variant	1/7		NP_001243405.1	Q96MX6-2
DNAAF10	NR_046234.2 linkuse as main transcript	n.154+52G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNAAF10	ENST00000295121.11 linkuse as main transcript	c.122G>A	p.Arg41Gln	missense_variant	1/8	1	NM_138458.4	ENSP00000295121.6	Q96MX6-1
ENSG00000273398	ENST00000406334.3 linkuse as main transcript	n.*139G>A		non_coding_transcript_exon_variant	8/15	2		ENSP00000384974.3	H7BYZ3
ENSG00000273398	ENST00000406334.3 linkuse as main transcript	n.*139G>A		3_prime_UTR_variant	8/15	2		ENSP00000384974.3	H7BYZ3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 09, 2024

The c.122G>A (p.R41Q) alteration is located in exon 1 (coding exon 1) of the WDR92 gene. This alteration results from a G to A substitution at nucleotide position 122, causing the arginine (R) at amino acid position 41 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.046

T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.055

MetaRNN

Uncertain

0.55

D;D

MetaSVM

Uncertain

-0.15

MutationAssessor

Pathogenic

2.9

M;M

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.6

D;D

REVEL

Uncertain

0.46

Sift

Uncertain

0.016

D;D

Sift4G

Uncertain

0.020

D;D

Polyphen

0.90

P;.

Vest4

0.59

MutPred

0.60

Loss of methylation at R41 (P = 0.0204);Loss of methylation at R41 (P = 0.0204);

MVP

0.37

MPC

0.39

ClinPred

0.98

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.57

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over