5-13865890-A-T

Variant names:

• chr5-13865890-A-T
• NM_001369.3:c.4133T>A

Variant summary

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

The NM_001369.3(DNAH5):​c.4133T>A​(p.Ile1378Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000623 in 1,444,380 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: DNAH5 NM_001369.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.31

Genes affected

DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]

ENSG00000251423 (HGNC:40187):

ACMG classification

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
DNAH5	NM_001369.3	c.4133T>A	p.Ile1378Asn	missense_variant	Exon 27 of 79	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.4133T>A	p.Ile1378Asn	missense_variant	Exon 27 of 79	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.4088T>A	p.Ile1363Asn	missense_variant	Exon 27 of 79			ENSP00000505288.1
ENSG00000251423	ENST00000503244.2	n.253+5335A>T		intron_variant	Intron 1 of 2	4
ENSG00000251423	ENST00000637153.1	n.213+5375A>T		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000623 AC: 9 AN: 1444380 Hom.: 0 Cov.: 30 AF XY: 0.00000695 AC XY: 5 AN XY: 719864

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: 0.00000821

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	Benign	0.17
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.59	D
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D
Polyphen		0.29	B
Vest4		0.75
MutPred		0.64		Loss of stability (P = 0.0504);
MVP		0.53
MPC		0.34
ClinPred		1.0	D
GERP RS		6.0
Varity_R		0.80
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-13865999;