Genetic Variant NM_001367479.1:c.13037T>A (chr1-225381539-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001367479.1(DNAH14):c.13037T>A(p.Phe4346Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F4346C) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNAH14
NM_001367479.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.88

Publications

24 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P

DNAH14 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036192656).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367479.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH14	NM_001367479.1	MANE Select	c.13037T>A	p.Phe4346Tyr	missense	Exon 81 of 86	NP_001354408.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAH14	ENST00000682510.1	MANE Select	c.13037T>A	p.Phe4346Tyr	missense	Exon 81 of 86	ENSP00000508305.1
DNAH14	ENST00000327794.10	TSL:1	n.*1248T>A		non_coding_transcript_exon	Exon 36 of 40	ENSP00000328980.6
DNAH14	ENST00000327794.10	TSL:1	n.*1248T>A		3_prime_UTR	Exon 36 of 40	ENSP00000328980.6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1389352

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

685170

African (AFR)

AF:

0.00

AC:

AN:

30694

American (AMR)

AF:

0.00

AC:

AN:

32468

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24940

East Asian (EAS)

AF:

0.00

AC:

AN:

35662

South Asian (SAS)

AF:

0.00

AC:

AN:

77096

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5670

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1075994

Other (OTH)

AF:

0.00

AC:

AN:

57618

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

8.9

(source)

DANN

Benign

0.33

DEOGEN2

Benign

0.0014

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.38

M_CAP

Benign

0.014

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.20

PhyloP100

2.9

PrimateAI

Benign

0.44

PROVEAN

Benign

1.7

REVEL

Benign

0.080

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.18

MutPred

0.49

Gain of catalytic residue at I4243 (P = 0.0428)

MVP

0.040

ClinPred

0.032

GERP RS

1.2

Varity_R

0.058

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over