chr16-20936689-C-G

Variant names:

• chr16-20936689-C-G
• rs1210733444
• NM_001347886.2:c.11681G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001347886.2(DNAH3):​c.11681G>C​(p.Gly3894Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DNAH3 NM_001347886.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41464502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH3	NM_001347886.2	c.11681G>C	p.Gly3894Ala	missense_variant	Exon 60 of 62	ENST00000698260.1	NP_001334815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH3	ENST00000698260.1	c.11681G>C	p.Gly3894Ala	missense_variant	Exon 60 of 62		NM_001347886.2	ENSP00000513632.1
DNAH3	ENST00000261383.3	c.11819G>C	p.Gly3940Ala	missense_variant	Exon 60 of 62	1		ENSP00000261383.3
DNAH3	ENST00000685858.1	c.11861G>C	p.Gly3954Ala	missense_variant	Exon 60 of 62			ENSP00000508756.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000420 AC: 1 AN: 238062 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 128834

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: 0.00000936

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454088 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722670

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: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.64	N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.13
Sift	Benign	0.072	T
Polyphen		0.83	P
Vest4		0.43
MutPred		0.50		Loss of ubiquitination at K3936 (P = 0.0747);
MVP		0.25
MPC		0.32
ClinPred		0.55	D
GERP RS		5.8
Varity_R		0.27
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: rs1210733444; hg19: chr16-20948011;