17-78423801-G-A

Position:

• chr17-78423801-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173628.4(DNAH17):​c.*105C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,449,870 control chromosomes in the GnomAD database, including 19,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (1985 hom., cov: 32)
  • Exomes 𝑓: 0.16 (17918 hom.)
• Consequence: DNAH17 NM_173628.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.284

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-78423801-G-A is Benign according to our data. Variant chr17-78423801-G-A is described in ClinVar as [Benign]. Clinvar id is 1246795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.*105C>T		3_prime_UTR_variant	81/81	ENST00000389840.7	NP_775899.3
PGS1	NM_024419.5	c.*11-260G>A		intron_variant		ENST00000262764.11	NP_077733.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7	c.*105C>T		3_prime_UTR_variant	81/81	5	NM_173628.4	ENSP00000374490	P1
PGS1	ENST00000262764.11	c.*11-260G>A		intron_variant		1	NM_024419.5	ENSP00000262764	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23761 AN: 152030 Hom.: 1982 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0308

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.162 AC: 209952 AN: 1297722 Hom.: 17918 Cov.: 19 AF XY: 0.162 AC XY: 103816 AN XY: 642298

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.0909

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.0217

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.156 AC: 23781 AN: 152148 Hom.: 1985 Cov.: 32 AF XY: 0.152 AC XY: 11279 AN XY: 74396

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.0306

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.162

Alfa AF: 0.159 Hom.: 339

Bravo AF: 0.159

Asia WGS AF: 0.0770 AC: 270 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.46
DANN	Benign	0.77

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: rs72903323; hg19: chr17-76419882;