Variant chr1-66833619-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024763.5(DNAI4):c.1979A>C(p.Gln660Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,324 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

DNAI4
NM_024763.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.48

Variant links:

Genes affected

DNAI4 (HGNC:26252): (dynein axonemal intermediate chain 4) Predicted to enable dynein heavy chain binding activity and dynein light chain binding activity. Predicted to be involved in axonemal dynein complex assembly and cilium movement. Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be located in axoneme; dynein axonemal particle; and motile cilium. Predicted to be part of axonemal dynein complex. [provided by Alliance of Genome Resources, Apr 2022]

DNAI4 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	UniProt
DNAI4	NM_024763.5 linkuse as main transcript	c.1979A>C	p.Gln660Pro	missense_variant	13/17	ENST00000371026.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAI4	ENST00000371026.8 linkuse as main transcript	c.1979A>C	p.Gln660Pro	missense_variant	13/17	1	NM_024763.5	P1	Q5VTH9-1
DNAI4	ENST00000464352.6 linkuse as main transcript	c.1277A>C	p.Gln426Pro	missense_variant	9/12	2
DNAI4	ENST00000491297.6 linkuse as main transcript	c.*1921A>C		3_prime_UTR_variant, NMD_transcript_variant	10/14	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

250736

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135528

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461190

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726878

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

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:

0.0000189

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000119

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

Mar 13, 2023

The c.1979A>C (p.Q660P) alteration is located in exon 13 (coding exon 13) of the WDR78 gene. This alteration results from a A to C substitution at nucleotide position 1979, causing the glutamine (Q) at amino acid position 660 to be replaced by a proline (P). 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

Uncertain

0.44

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.051

T;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.88

D;T

M_CAP

Benign

0.042

MetaRNN

Uncertain

0.45

T;T

MetaSVM

Benign

-0.55

MutationAssessor

Benign

2.0

M;.

MutationTaster

Benign

0.90

D;D

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-4.0

D;D

REVEL

Benign

0.21

Sift

Benign

0.18

T;T

Sift4G

Benign

0.096

T;D

Polyphen

1.0

D;.

Vest4

0.75

MutPred

0.38

Gain of glycosylation at S658 (P = 0.06);.;

MVP

0.69

MPC

0.51

ClinPred

0.88

GERP RS

5.8

Varity_R

0.60

gMVP

0.58

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