NM_173628.4:c.13303A>C

Variant names:

• chr17-78423992-T-G
• NM_173628.4:c.13303A>C

Variant summary

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

The NM_173628.4(DNAH17):​c.13303A>C​(p.Thr4435Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,696 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: DNAH17 NM_173628.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.51

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]

PGS1 (HGNC:30029): (phosphatidylglycerophosphate synthase 1) Predicted to enable CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase activity and calcium ion binding activity. Predicted to be involved in cardiolipin biosynthetic process and diacylglycerol metabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

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, 0.769

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.13303A>C	p.Thr4435Pro	missense_variant	Exon 81 of 81	ENST00000389840.7	NP_775899.3
PGS1	NM_024419.5	c.*11-69T>G		intron_variant	Intron 9 of 9	ENST00000262764.11	NP_077733.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7	c.13303A>C	p.Thr4435Pro	missense_variant	Exon 81 of 81	5	NM_173628.4	ENSP00000374490.6
PGS1	ENST00000262764.11	c.*11-69T>G		intron_variant	Intron 9 of 9	1	NM_024419.5	ENSP00000262764.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461696 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727132

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: 8.99e-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	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	26
DANN	Uncertain	1.0
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.042	D
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Benign	-0.61	T
PrimateAI	Uncertain	0.63	T
REVEL	Uncertain	0.43
Vest4		0.65
MVP		0.34
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.57
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-76420073;