chr17-78437816-T-G

Position:

• chr17-78437816-T-G

Variant summary

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

The NM_173628.4(DNAH17):​c.11858A>C​(p.His3953Pro) 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. 12/18 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. H3953R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DNAH17 NM_173628.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

Genes affected

DNAH17 (HGNC:2946): (dynein axonemal heavy chain 17) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. DNAH17 is a heavy chain associated with axonemal dynein (Milisav and Affara, 1998 [PubMed 9545504]).[supplied by OMIM, Mar 2008]

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=0.15377864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH17	NM_173628.4	c.11858A>C	p.His3953Pro	missense_variant	74/81	ENST00000389840.7
DNAH17	XM_011525416.3	c.11870A>C	p.His3957Pro	missense_variant	74/81
DNAH17	XM_024451013.2	c.11726A>C	p.His3909Pro	missense_variant	73/80

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH17	ENST00000389840.7	c.11858A>C	p.His3953Pro	missense_variant	74/81	5	NM_173628.4	P1
DNAH17	ENST00000586052.5	n.4994A>C		non_coding_transcript_exon_variant	28/35	5
DNAH17	ENST00000590227.5	n.1532A>C		non_coding_transcript_exon_variant	6/13	2
DNAH17	ENST00000591369.5	c.3461A>C	p.His1154Pro	missense_variant, NMD_transcript_variant	21/28	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.95
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.34	T
Vest4		0.23
MVP		0.15
ClinPred		0.22	T
GERP RS		4.1
Varity_R		0.85
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

LitVar

Other links and lift over

dbSNP: rs12941494; hg19: chr17-76433898;