Variant 1-225377313-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001367479.1(DNAH14):c.12593T>C(p.Leu4198Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 1,548,846 control chromosomes in the GnomAD database, including 317,763 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 27332 hom., cov: 32)

Exomes 𝑓: 0.64 ( 290431 hom. )

Consequence

DNAH14
NM_001367479.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.80

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.33696E-6).

BP6

Variant 1-225377313-T-C is Benign according to our data. Variant chr1-225377313-T-C is described in ClinVar as [Benign]. Clinvar id is 402664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.745 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.12593T>C	p.Leu4198Pro	missense_variant	79/86	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.12593T>C	p.Leu4198Pro	missense_variant	79/86		NM_001367479.1	ENSP00000508305.1		A0A804HLD3

Frequencies

GnomAD3 genomes

AF:

0.581

AC:

88326

AN:

151904

Hom.:

27315

Cov.:

show subpopulations

Gnomad AFR

AF:

0.356

Gnomad AMI

AF:

0.550

Gnomad AMR

AF:

0.726

Gnomad ASJ

AF:

0.706

Gnomad EAS

AF:

0.764

Gnomad SAS

AF:

0.460

Gnomad FIN

AF:

0.694

Gnomad MID

AF:

0.706

Gnomad NFE

AF:

0.656

Gnomad OTH

AF:

0.623

GnomAD3 exomes

AF:

0.638

AC:

97070

AN:

152100

Hom.:

32155

AF XY:

0.626

AC XY:

50507

AN XY:

80730

show subpopulations

Gnomad AFR exome

AF:

0.346

Gnomad AMR exome

AF:

0.746

Gnomad ASJ exome

AF:

0.703

Gnomad EAS exome

AF:

0.759

Gnomad SAS exome

AF:

0.466

Gnomad FIN exome

AF:

0.689

Gnomad NFE exome

AF:

0.651

Gnomad OTH exome

AF:

0.682

GnomAD4 exome

AF:

0.640

AC:

894053

AN:

1396824

Hom.:

290431

Cov.:

AF XY:

0.635

AC XY:

437648

AN XY:

688832

show subpopulations

Gnomad4 AFR exome

AF:

0.331

Gnomad4 AMR exome

AF:

0.745

Gnomad4 ASJ exome

AF:

0.705

Gnomad4 EAS exome

AF:

0.780

Gnomad4 SAS exome

AF:

0.469

Gnomad4 FIN exome

AF:

0.690

Gnomad4 NFE exome

AF:

0.649

Gnomad4 OTH exome

AF:

0.640

GnomAD4 genome

AF:

0.581

AC:

88371

AN:

152022

Hom.:

27332

Cov.:

AF XY:

0.585

AC XY:

43442

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.355

Gnomad4 AMR

AF:

0.726

Gnomad4 ASJ

AF:

0.706

Gnomad4 EAS

AF:

0.765

Gnomad4 SAS

AF:

0.461

Gnomad4 FIN

AF:

0.694

Gnomad4 NFE

AF:

0.656

Gnomad4 OTH

AF:

0.629

Alfa

AF:

0.651

Hom.:

75378

Bravo

AF:

0.580

TwinsUK

AF:

0.643

AC:

2385

ALSPAC

AF:

0.656

AC:

2529

ESP6500AA

AF:

0.342

AC:

474

ESP6500EA

AF:

0.657

AC:

2091

ExAC

AF:

0.542

AC:

11668

Asia WGS

AF:

0.590

AC:

2052

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.040

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.00080

T;.;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.00024

LIST_S2

Benign

0.13

T;T;.

MetaRNN

Benign

0.0000013

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.1

N;.;.

PrimateAI

Benign

0.39

PROVEAN

Benign

1.5

N;N;N

REVEL

Benign

0.061

Sift

Benign

0.33

T;T;T

Sift4G

Benign

0.17

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.041

ClinPred

0.0032

GERP RS

4.3

Varity_R

0.071

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