Variant 11-6498499-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_144666.3(DNHD1):c.284G>A(p.Arg95His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,614,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

DNHD1
NM_144666.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40

Variant links:

Genes affected

DNHD1 (HGNC:26532): (dynein heavy chain domain 1) Predicted to enable dynein intermediate chain binding activity; dynein light intermediate chain binding activity; and minus-end-directed microtubule motor activity. Predicted to be involved in cilium movement. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

DNHD1 links:

DNHD1 (HGNC:):

DNHD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DNHD1. . Gene score misZ 3.4791 (greater than the threshold 3.09). Trascript score misZ 3.2933 (greater than threshold 3.09). GenCC has associacion of gene with spermatogenic failure 65.

BP4

Computational evidence support a benign effect (MetaRNN=0.15016055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNHD1	NM_144666.3 linkuse as main transcript	c.284G>A	p.Arg95His	missense_variant	3/43	ENST00000254579.11	NP_653267.2	Q96M86-3B0I1S4
DNHD1	NM_173589.4 linkuse as main transcript	c.284G>A	p.Arg95His	missense_variant	2/8		NP_775860.3	Q96M86-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNHD1	ENST00000254579.11 linkuse as main transcript	c.284G>A	p.Arg95His	missense_variant	3/43	5	NM_144666.3	ENSP00000254579.6		Q96M86-3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251342

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000349

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2023

The c.284G>A (p.R95H) alteration is located in exon 3 (coding exon 1) of the DNHD1 gene. This alteration results from a G to A substitution at nucleotide position 284, causing the arginine (R) at amino acid position 95 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0096

T;.;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.67

T;T;.

M_CAP

Benign

0.0098

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

L;L;L

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.11

Sift

Uncertain

0.022

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.17

MVP

0.46

MPC

0.23

ClinPred

0.65

GERP RS

4.4

Varity_R

0.085

gMVP

0.17

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