Variant 16-4740318-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139170.3(DNAAF8):c.442G>A(p.Glu148Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,868 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

DNAAF8
NM_139170.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.680

Variant links:

Genes affected

DNAAF8 (HGNC:25081): (dynein axonemal assembly factor 8) Predicted to enable dynein complex binding activity. Predicted to be involved in outer dynein arm assembly. Located in dynein axonemal particle. [provided by Alliance of Genome Resources, Apr 2022]

DNAAF8 links:

DNAAF8 (HGNC:):

DNAAF8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10858238).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF8	NM_139170.3 linkuse as main transcript	c.442G>A	p.Glu148Lys	missense_variant	4/10	ENST00000299320.10	NP_631909.2	Q8IYS4
DNAAF8	XM_017022975.2 linkuse as main transcript	c.511G>A	p.Glu171Lys	missense_variant	4/10		XP_016878464.1
DNAAF8	XM_005255144.4 linkuse as main transcript	c.28G>A	p.Glu10Lys	missense_variant	3/9		XP_005255201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF8	ENST00000299320.10 linkuse as main transcript	c.442G>A	p.Glu148Lys	missense_variant	4/10	1	NM_139170.3	ENSP00000299320.4		Q8IYS4

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251324

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000752

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152032

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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

Bravo

AF:

0.00000378

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

Sep 16, 2021

The c.442G>A (p.E148K) alteration is located in exon 4 (coding exon 3) of the C16orf71 gene. This alteration results from a G to A substitution at nucleotide position 442, causing the glutamic acid (E) at amino acid position 148 to be replaced by a lysine (K). 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

0.11

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0019

T;.;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.55

T;T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.59

N;.;.

PROVEAN

Benign

-2.3

N;.;.

REVEL

Benign

0.012

Sift

Uncertain

0.0090

D;.;.

Sift4G

Benign

0.20

T;T;T

Polyphen

0.11

B;.;.

Vest4

0.16

MutPred

0.23

Gain of ubiquitination at E148 (P = 0.0066);Gain of ubiquitination at E148 (P = 0.0066);.;

MVP

0.030

MPC

0.021

ClinPred

0.094

GERP RS

2.1

Varity_R

0.16

gMVP

0.091

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

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