rs193921090

chr16-21000377-G-Achr16-21000377-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001347886.2(DNAH3):c.6130C>T(p.His2044Tyr) 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. 14/21 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. H2044N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAH3 NM_001347886.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.700

Genes affected

DNAH3 (HGNC:2949): (dynein axonemal heavy chain 3) This gene belongs to the dynein family, whose members encode large proteins that are constituents of the microtubule-associated motor protein complex. This complex is composed of dynein heavy, intermediate and light chains, which can be axonemal or cytoplasmic. This protein is an axonemal dynein heavy chain. It is involved in producing force for ciliary beating by using energy from ATP hydrolysis. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20040789).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH3	NM_001347886.2	c.6130C>T	p.His2044Tyr	missense_variant	43/62	ENST00000698260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH3	ENST00000698260.1	c.6130C>T	p.His2044Tyr	missense_variant	43/62		NM_001347886.2	P1
DNAH3	ENST00000261383.3	c.6268C>T	p.His2090Tyr	missense_variant	43/62	1
DNAH3	ENST00000685858.1	c.6310C>T	p.His2104Tyr	missense_variant	43/62
DNAH3	ENST00000572640.5	n.2979C>T		non_coding_transcript_exon_variant	20/21	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	18
Dann	Uncertain	0.99
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.097
Sift	Uncertain	0.026	D
Polyphen		0.25	B
Vest4		0.29
MutPred		0.34		Gain of ubiquitination at K2093 (P = 0.1278);
MVP		0.20
MPC		0.11
ClinPred		0.50	T
GERP RS		4.8
Varity_R		0.16
gMVP		0.30

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

Other links and lift over

dbSNP: rs193921090; hg19: chr16-21011699; COSMIC: COSV54514883;