17-78424017-C-A

Variant names:

• chr17-78424017-C-A
• rs138312957
• NM_173628.4:c.13278G>T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_173628.4(DNAH17):​c.13278G>T​(p.Val4426Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00405 in 1,614,038 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0041 (19 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• 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]

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 17-78424017-C-A is Benign according to our data. Variant chr17-78424017-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2648343.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78424017-C-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.135 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00328 (500/152334) while in subpopulation NFE AF= 0.00439 (299/68040). AF 95% confidence interval is 0.00398. There are 0 homozygotes in gnomad4. There are 257 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.13278G>T	p.Val4426Val	synonymous_variant	Exon 81 of 81	ENST00000389840.7	NP_775899.3
PGS1	NM_024419.5	c.*11-44C>A		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.13278G>T	p.Val4426Val	synonymous_variant	Exon 81 of 81	5	NM_173628.4	ENSP00000374490.6
PGS1	ENST00000262764.11	c.*11-44C>A		intron_variant	Intron 9 of 9	1	NM_024419.5	ENSP00000262764.5

Frequencies

GnomAD3 genomes AF: 0.00328 AC: 500 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000844

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00426

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00857

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00439

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00354 AC: 884 AN: 249600 Hom.: 5 AF XY: 0.00341 AC XY: 460 AN XY: 135058

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.00228

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00832

Gnomad NFE exome AF: 0.00532

Gnomad OTH exome AF: 0.00327

GnomAD4 exome AF: 0.00413 AC: 6033 AN: 1461704 Hom.: 19 Cov.: 31 AF XY: 0.00398 AC XY: 2891 AN XY: 727134

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.00246

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00908

Gnomad4 NFE exome AF: 0.00466

Gnomad4 OTH exome AF: 0.00398

GnomAD4 genome AF: 0.00328 AC: 500 AN: 152334 Hom.: 0 Cov.: 33 AF XY: 0.00345 AC XY: 257 AN XY: 74486

Gnomad4 AFR AF: 0.000842

Gnomad4 AMR AF: 0.00425

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00857

Gnomad4 NFE AF: 0.00439

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00384 Hom.: 0

Bravo AF: 0.00287

EpiCase AF: 0.00393

EpiControl AF: 0.00462

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

DNAH17-related disorder Benign:1

Mar 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DNAH17: BP4, BP7, BS2; PGS1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	1.5
DANN	Benign	0.84

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: rs138312957; hg19: chr17-76420098; COSMIC: COSV53148692; COSMIC: COSV53148692;