7-754620-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_017802.4(DNAAF5):c.1056C>T(p.Leu352Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 1,614,096 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0093 ( 16 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 30 hom. )

Consequence

DNAAF5
NM_017802.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.826

Variant links:

Genes affected

DNAAF5 (HGNC:26013): (dynein axonemal assembly factor 5) The protein encoded by this gene is essential for the preassembly or stability of axonemal dynein arms, and is found only in organisms with motile cilia and flagella. Mutations in this gene are associated with primary ciliary dyskinesia-18, a disorder characterized by abnormalities of motile cilia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]

DNAAF5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 7-754620-C-T is Benign according to our data. Variant chr7-754620-C-T is described in ClinVar as [Benign]. Clinvar id is 260921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.826 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00933 (1421/152282) while in subpopulation AFR AF= 0.0212 (880/41556). AF 95% confidence interval is 0.02. There are 16 homozygotes in gnomad4. There are 634 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF5	NM_017802.4 link	c.1056C>T	p.Leu352Leu	synonymous_variant	Exon 5 of 13	ENST00000297440.11	NP_060272.3	Q86Y56-1B3KPE2
DNAAF5	XM_024446813.2 link	c.1056C>T	p.Leu352Leu	synonymous_variant	Exon 5 of 12		XP_024302581.1
DNAAF5	NR_075098.2 link	n.1016C>T		non_coding_transcript_exon_variant	Exon 5 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAAF5	ENST00000297440.11 link	c.1056C>T	p.Leu352Leu	synonymous_variant	Exon 5 of 13	1	NM_017802.4	ENSP00000297440.6	Q86Y56-1
DNAAF5	ENST00000440747.5 link	c.459C>T	p.Leu153Leu	synonymous_variant	Exon 5 of 13	2		ENSP00000403165.1	H0Y650
DNAAF5	ENST00000437419.5 link	c.372C>T	p.Leu124Leu	synonymous_variant	Exon 4 of 5	5		ENSP00000410788.1	H7C3B1

Frequencies

GnomAD3 genomes

AF:

0.00934

AC:

1421

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0212

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.00857

Gnomad ASJ

AF:

0.0185

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00332

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00476

AC:

1195

AN:

251074

Hom.:

AF XY:

0.00422

AC XY:

572

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.0232

Gnomad AMR exome

AF:

0.00709

Gnomad ASJ exome

AF:

0.0146

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.000817

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.00291

Gnomad OTH exome

AF:

0.00767

GnomAD4 exome

AF:

0.00304

AC:

4446

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00295

AC XY:

2145

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.0208

Gnomad4 AMR exome

AF:

0.00702

Gnomad4 ASJ exome

AF:

0.0154

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.000626

Gnomad4 FIN exome

AF:

0.000506

Gnomad4 NFE exome

AF:

0.00225

Gnomad4 OTH exome

AF:

0.00616

GnomAD4 genome

AF:

0.00933

AC:

1421

AN:

152282

Hom.:

Cov.:

AF XY:

0.00852

AC XY:

634

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0212

Gnomad4 AMR

AF:

0.00856

Gnomad4 ASJ

AF:

0.0185

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.00332

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.00646

Hom.:

Bravo

AF:

0.0106

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:2

Aug 19, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 18

Benign:1

Jul 08, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.67

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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