Variant 1-224964551-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001367479.1(DNAH14):c.440C>T(p.Pro147Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0076 in 1,608,164 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0063 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0077 ( 63 hom. )

Consequence

DNAH14
NM_001367479.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.607

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048256814).

BP6

Variant 1-224964551-C-T is Benign according to our data. Variant chr1-224964551-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639939.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH14	NM_001367479.1 linkuse as main transcript	c.440C>T	p.Pro147Leu	missense_variant	5/86	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.440C>T	p.Pro147Leu	missense_variant	5/86		NM_001367479.1	ENSP00000508305	P1

Frequencies

GnomAD3 genomes

AF:

0.00629

AC:

956

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00392

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00440

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00331

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00887

Gnomad OTH

AF:

0.00768

GnomAD3 exomes

AF:

0.00584

AC:

1454

AN:

248858

Hom.:

AF XY:

0.00588

AC XY:

794

AN XY:

135006

show subpopulations

Gnomad AFR exome

AF:

0.00388

Gnomad AMR exome

AF:

0.00329

Gnomad ASJ exome

AF:

0.00785

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.00246

Gnomad FIN exome

AF:

0.00311

Gnomad NFE exome

AF:

0.00907

Gnomad OTH exome

AF:

0.00546

GnomAD4 exome

AF:

0.00773

AC:

11261

AN:

1456106

Hom.:

Cov.:

AF XY:

0.00750

AC XY:

5430

AN XY:

724238

show subpopulations

Gnomad4 AFR exome

AF:

0.00240

Gnomad4 AMR exome

AF:

0.00363

Gnomad4 ASJ exome

AF:

0.00923

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00255

Gnomad4 FIN exome

AF:

0.00416

Gnomad4 NFE exome

AF:

0.00890

Gnomad4 OTH exome

AF:

0.00756

GnomAD4 genome

AF:

0.00629

AC:

957

AN:

152058

Hom.:

Cov.:

AF XY:

0.00599

AC XY:

445

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.00390

Gnomad4 AMR

AF:

0.00439

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00331

Gnomad4 NFE

AF:

0.00889

Gnomad4 OTH

AF:

0.00760

Alfa

AF:

0.00796

Hom.:

Bravo

AF:

0.00589

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.00652

AC:

ExAC

AF:

0.00591

AC:

714

Asia WGS

AF:

0.00145

AC:

AN:

3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

DNAH14: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.031

T;.;.;.;.;.;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.66

T;T;T;T;T;.;.

M_CAP

Benign

0.0089

MetaRNN

Benign

0.0048

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.8

D;D;D;D;D;D;D

REVEL

Benign

0.050

Sift

Benign

0.19

T;T;T;T;T;T;T

Sift4G

Uncertain

0.013

D;D;T;T;T;T;D

Polyphen

0.013

B;B;B;B;.;B;B

Vest4

0.15

MVP

0.38

MPC

0.056

ClinPred

0.010

GERP RS

0.60

Varity_R

0.059

gMVP

0.23

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