rs761168416

Variant names:

• chr5-13870780-A-C
• NM_001369.3:c.3821T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-13870780-A-C
• chr5-13870780-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001369.3(DNAH5):​c.3821T>G​(p.Val1274Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: DNAH5 NM_001369.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.91

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.791

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.3821T>G	p.Val1274Gly	missense_variant	Exon 24 of 79	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.3821T>G	p.Val1274Gly	missense_variant	Exon 24 of 79	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.3776T>G	p.Val1259Gly	missense_variant	Exon 24 of 79			ENSP00000505288.1
ENSG00000251423	ENST00000503244.2	n.253+10225A>C		intron_variant	Intron 1 of 2	4
ENSG00000251423	ENST00000637153.1	n.213+10265A>C		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460746 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726744

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: 9.00e-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	Benign	0.19
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.58	D
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.065	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0010	D
Polyphen		0.35	B
Vest4		0.55
MutPred		0.79		Gain of disorder (P = 0.0169);
MVP		0.56
MPC		0.23
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.79
gMVP		0.81

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: chr5-13870889;