3-52349229-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015512.5(DNAH1):​c.2335G>T​(p.Val779Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,544 control chromosomes in the GnomAD database, with no homozygous occurrence. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DNAH1
NM_015512.5 missense

Scores

1
2
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.42
Variant links:
Genes affected
DNAH1 (HGNC:2940): (dynein axonemal heavy chain 1) This gene encodes an inner dynein arm heavy chain that provides structural support between the radial spokes and the outer doublet of the sperm tail. Naturally occurring mutations in this gene are associated with primary ciliary dyskinesia and multiple morphological anomalies of the flagella that result in asthenozoospermia and male infertility. Mice with a homozygous knockout of the orthologous gene are viable but have reduced sperm motility and are infertile. [provided by RefSeq, Feb 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAH1NM_015512.5 linkc.2335G>T p.Val779Leu missense_variant Exon 14 of 78 ENST00000420323.7 NP_056327.4 Q9P2D7-4A0A140VJI6
DNAH1XM_017006129.2 linkc.2335G>T p.Val779Leu missense_variant Exon 15 of 80 XP_016861618.1
DNAH1XM_017006130.2 linkc.2335G>T p.Val779Leu missense_variant Exon 15 of 79 XP_016861619.1 Q9P2D7-4A0A140VJI6
DNAH1XM_017006131.2 linkc.2335G>T p.Val779Leu missense_variant Exon 15 of 79 XP_016861620.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAH1ENST00000420323.7 linkc.2335G>T p.Val779Leu missense_variant Exon 14 of 78 1 NM_015512.5 ENSP00000401514.2 Q9P2D7-4
DNAH1ENST00000486752.5 linkn.2596G>T non_coding_transcript_exon_variant Exon 14 of 77 2
DNAH1ENST00000497875.1 linkn.2500G>T non_coding_transcript_exon_variant Exon 15 of 21 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461544
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
727062
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.34
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
22
DANN
Benign
0.83
Eigen
Benign
0.015
Eigen_PC
Benign
0.16
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.76
T
M_CAP
Benign
0.0059
T
MetaRNN
Uncertain
0.46
T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-0.93
N
REVEL
Benign
0.12
Sift
Benign
0.69
T
Sift4G
Benign
0.61
T
Vest4
0.58
MutPred
0.65
Loss of helix (P = 0.2022);
MVP
0.38
MPC
0.12
ClinPred
0.50
T
GERP RS
5.5
gMVP
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-52383245; API