Variant 17-78423903-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_173628.4(DNAH17):c.*3C>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 0.00645 in 1,613,820 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0051 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0066 ( 57 hom. )

Consequence

DNAH17
NM_173628.4 3_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.295

Variant links:

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]

DNAH17 links:

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]

PGS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-78423903-G-A is Benign according to our data. Variant chr17-78423903-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3033897.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00509 (775/152350) while in subpopulation NFE AF= 0.00717 (488/68022). AF 95% confidence interval is 0.00665. There are 5 homozygotes in gnomad4. There are 413 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH17	NM_173628.4 linkuse as main transcript	c.*3C>T		3_prime_UTR_variant	81/81	ENST00000389840.7	NP_775899.3
PGS1	NM_024419.5 linkuse as main transcript	c.*11-158G>A		intron_variant		ENST00000262764.11	NP_077733.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7 linkuse as main transcript	c.*3C>T		3_prime_UTR_variant	81/81	5	NM_173628.4	ENSP00000374490	P1	Q9UFH2-1
PGS1	ENST00000262764.11 linkuse as main transcript	c.*11-158G>A		intron_variant		1	NM_024419.5	ENSP00000262764	P1	Q32NB8-1

Frequencies

GnomAD3 genomes

AF:

0.00509

AC:

775

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0158

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00717

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.00586

AC:

1470

AN:

250904

Hom.:

AF XY:

0.00583

AC XY:

790

AN XY:

135616

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.00274

Gnomad FIN exome

AF:

0.0140

Gnomad NFE exome

AF:

0.00859

Gnomad OTH exome

AF:

0.00669

GnomAD4 exome

AF:

0.00660

AC:

9642

AN:

1461470

Hom.:

Cov.:

AF XY:

0.00645

AC XY:

4689

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.00152

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00126

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.00254

Gnomad4 FIN exome

AF:

0.0137

Gnomad4 NFE exome

AF:

0.00742

Gnomad4 OTH exome

AF:

0.00505

GnomAD4 genome

AF:

0.00509

AC:

775

AN:

152350

Hom.:

Cov.:

AF XY:

0.00554

AC XY:

413

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00190

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.0158

Gnomad4 NFE

AF:

0.00717

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00576

Hom.:

Bravo

AF:

0.00371

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00709

EpiControl

AF:

0.00557

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PGS1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 01, 2019

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.77

DANN

Benign

0.59

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over