Variant rs12742757 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001367479.1(DNAH14):c.10746T>A(p.Ile3582Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0876 in 1,551,380 control chromosomes in the GnomAD database, including 7,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1173 hom., cov: 32)

Exomes 𝑓: 0.085 ( 6551 hom. )

Consequence

DNAH14
NM_001367479.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.813

Variant links:

Genes affected

DNAH14 (HGNC:2945): (dynein axonemal heavy chain 14) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. Two major classes of dyneins, axonemal and cytoplasmic, have been identified. DNAH14 is an axonemal dynein heavy chain (DHC) (Vaughan et al., 1996 [PubMed 8812413]).[supplied by OMIM, Mar 2008]

DNAH14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 1-225346029-T-A is Benign according to our data. Variant chr1-225346029-T-A is described in ClinVar as [Benign]. Clinvar id is 402658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.813 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH14	NM_001367479.1 linkuse as main transcript	c.10746T>A	p.Ile3582Ile	synonymous_variant	70/86	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1 linkuse as main transcript	c.10746T>A	p.Ile3582Ile	synonymous_variant	70/86		NM_001367479.1	ENSP00000508305.1		A0A804HLD3

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17255

AN:

151948

Hom.:

1170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.0502

Gnomad EAS

AF:

0.258

Gnomad SAS

AF:

0.0902

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0749

Gnomad OTH

AF:

0.105

GnomAD3 exomes

AF:

0.120

AC:

18615

AN:

155208

Hom.:

1588

AF XY:

0.112

AC XY:

9217

AN XY:

82312

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.226

Gnomad ASJ exome

AF:

0.0478

Gnomad EAS exome

AF:

0.271

Gnomad SAS exome

AF:

0.0751

Gnomad FIN exome

AF:

0.134

Gnomad NFE exome

AF:

0.0709

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.0848

AC:

118628

AN:

1399316

Hom.:

6551

Cov.:

AF XY:

0.0841

AC XY:

58012

AN XY:

690176

show subpopulations

Gnomad4 AFR exome

AF:

0.149

Gnomad4 AMR exome

AF:

0.216

Gnomad4 ASJ exome

AF:

0.0485

Gnomad4 EAS exome

AF:

0.277

Gnomad4 SAS exome

AF:

0.0745

Gnomad4 FIN exome

AF:

0.135

Gnomad4 NFE exome

AF:

0.0713

Gnomad4 OTH exome

AF:

0.0929

GnomAD4 genome

AF:

0.114

AC:

17275

AN:

152064

Hom.:

1173

Cov.:

AF XY:

0.119

AC XY:

8819

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.164

Gnomad4 ASJ

AF:

0.0502

Gnomad4 EAS

AF:

0.257

Gnomad4 SAS

AF:

0.0884

Gnomad4 FIN

AF:

0.139

Gnomad4 NFE

AF:

0.0749

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.0832

Hom.:

213

Bravo

AF:

0.118

Asia WGS

AF:

0.170

AC:

591

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 11, 2022	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

6.2

DANN

Benign

0.68

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