rs3128652

chr1-225080644-G-Achr1-225080644-G-Cchr1-225080644-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001367479.1(DNAH14):c.3032G>A(p.Arg1011Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 1,551,374 control chromosomes in the GnomAD database, including 663,935 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.80 ( 51621 hom., cov: 33)

Exomes 𝑓: 0.93 ( 612314 hom. )

Consequence

DNAH14
NM_001367479.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.59

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.8557279E-6).

BP6

Variant 1-225080644-G-A is Benign according to our data. Variant chr1-225080644-G-A is described in ClinVar as [Benign]. Clinvar id is 402648.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH14	NM_001367479.1 linkuse as main transcript	c.3032G>A	p.Arg1011Gln	missense_variant	19/86	ENST00000682510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH14	ENST00000682510.1 linkuse as main transcript	c.3032G>A	p.Arg1011Gln	missense_variant	19/86		NM_001367479.1	P1
DNAH14	ENST00000430092.5 linkuse as main transcript	c.3032G>A	p.Arg1011Gln	missense_variant	19/84	5			Q0VDD8-4
DNAH14	ENST00000439375.6 linkuse as main transcript	c.3032G>A	p.Arg1011Gln	missense_variant	18/83	5			Q0VDD8-4
DNAH14	ENST00000445597.6 linkuse as main transcript	c.2834G>A	p.Arg945Gln	missense_variant	15/61	5			Q0VDD8-1

Frequencies

GnomAD3 genomes

AF:

0.797

AC:

121013

AN:

151750

Hom.:

51603

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.980

Gnomad AMR

AF:

0.796

Gnomad ASJ

AF:

0.916

Gnomad EAS

AF:

0.715

Gnomad SAS

AF:

0.850

Gnomad FIN

AF:

0.967

Gnomad MID

AF:

0.845

Gnomad NFE

AF:

0.962

Gnomad OTH

AF:

0.824

GnomAD3 exomes

AF:

0.869

AC:

137287

AN:

157894

Hom.:

61078

AF XY:

0.879

AC XY:

73250

AN XY:

83304

show subpopulations

Gnomad AFR exome

AF:

0.471

Gnomad AMR exome

AF:

0.759

Gnomad ASJ exome

AF:

0.927

Gnomad EAS exome

AF:

0.702

Gnomad SAS exome

AF:

0.869

Gnomad FIN exome

AF:

0.970

Gnomad NFE exome

AF:

0.960

Gnomad OTH exome

AF:

0.891

GnomAD4 exome

AF:

0.931

AC:

1302663

AN:

1399506

Hom.:

612314

Cov.:

AF XY:

0.931

AC XY:

642618

AN XY:

690238

show subpopulations

Gnomad4 AFR exome

AF:

0.455

Gnomad4 AMR exome

AF:

0.766

Gnomad4 ASJ exome

AF:

0.926

Gnomad4 EAS exome

AF:

0.738

Gnomad4 SAS exome

AF:

0.869

Gnomad4 FIN exome

AF:

0.968

Gnomad4 NFE exome

AF:

0.962

Gnomad4 OTH exome

AF:

0.894

GnomAD4 genome

AF:

0.797

AC:

121067

AN:

151868

Hom.:

51621

Cov.:

AF XY:

0.797

AC XY:

59174

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.472

Gnomad4 AMR

AF:

0.796

Gnomad4 ASJ

AF:

0.916

Gnomad4 EAS

AF:

0.716

Gnomad4 SAS

AF:

0.852

Gnomad4 FIN

AF:

0.967

Gnomad4 NFE

AF:

0.962

Gnomad4 OTH

AF:

0.824

Alfa

AF:

0.925

Hom.:

93807

Bravo

AF:

0.769

TwinsUK

AF:

0.960

AC:

3560

ALSPAC

AF:

0.955

AC:

3679

ESP6500AA

AF:

0.519

AC:

718

ESP6500EA

AF:

0.961

AC:

3057

ExAC

AF:

0.859

AC:

21026

Asia WGS

AF:

0.753

AC:

2622

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

Cadd

Benign

0.012

Dann

Benign

0.71

DEOGEN2

Benign

0.0036

T;.;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.24

T;T;.

MetaRNN

Benign

0.0000029

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.29

PROVEAN

Benign

0.19

N;N;N

REVEL

Benign

0.0060

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.51

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.073

ClinPred

0.00069

GERP RS

-6.7

Varity_R

0.018

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