17-78424004-T-C

Variant names:

• chr17-78424004-T-C
• rs78023288
• NM_173628.4:c.13291A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173628.4(DNAH17):​c.13291A>G​(p.Ile4431Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00372 in 1,614,026 control chromosomes in the GnomAD database, including 254 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (31 hom., cov: 33)
  • Exomes 𝑓: 0.0036 (223 hom.)
• Consequence: DNAH17 NM_173628.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.00800
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002858162).
• BP6: Variant 17-78424004-T-C is Benign according to our data. Variant chr17-78424004-T-C is described in ClinVar as Benign. ClinVar VariationId is 1241586.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0896 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173628.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	NM_173628.4	MANE Select	c.13291A>G	p.Ile4431Val	missense	Exon 81 of 81	NP_775899.3	Q9UFH2-1
	PGS1	NM_024419.5	MANE Select	c.*11-57T>C		intron	N/A	NP_077733.3
	PGS1	NR_110601.2		n.1548-57T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.13291A>G	p.Ile4431Val	missense	Exon 81 of 81	ENSP00000374490.6	Q9UFH2-1
	PGS1	ENST00000262764.11	TSL:1 MANE Select	c.*11-57T>C		intron	N/A	ENSP00000262764.5	Q32NB8-1
	PGS1	ENST00000588281.5	TSL:1	n.1280-57T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00497 AC: 756 AN: 152206 Hom.: 31 Cov.: 33

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0966

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.0105 AC: 2631 AN: 249740 AF XY: 0.00908

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.0202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.100

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000134

Gnomad OTH exome AF: 0.00539

GnomAD4 exome AF: 0.00359 AC: 5252 AN: 1461702 Hom.: 223 Cov.: 31 AF XY: 0.00343 AC XY: 2494 AN XY: 727134

African (AFR) AF: 0.000269 AC: 9 AN: 33480

American (AMR) AF: 0.0203 AC: 908 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0960 AC: 3813 AN: 39700

South Asian (SAS) AF: 0.00154 AC: 133 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53398

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000729 AC: 81 AN: 1111866

Other (OTH) AF: 0.00500 AC: 302 AN: 60372

GnomAD4 genome AF: 0.00494 AC: 753 AN: 152324 Hom.: 31 Cov.: 33 AF XY: 0.00567 AC XY: 422 AN XY: 74486

African (AFR) AF: 0.000601 AC: 25 AN: 41568

American (AMR) AF: 0.0130 AC: 199 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0966 AC: 501 AN: 5186

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68036

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00472 Hom.: 77

Bravo AF: 0.00691

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00925 AC: 1123

Asia WGS AF: 0.0280 AC: 97 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	DNAH17-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.2
DANN	Benign	0.94
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-0.92	T
PhyloP100		-0.0080
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.017
Sift	Benign	0.33	T
Vest4		0.11
ClinPred		0.0017	T
GERP RS		0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.13
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs78023288; hg19: chr17-76420085; COSMIC: COSV53143127; COSMIC: COSV53143127;