NM_173628.4:c.*3C>T

Variant names:

• chr17-78423903-G-A
• rs72914863
• NM_173628.4:c.*3C>T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

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
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.295

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 -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 rank	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.*3C>T		3_prime_UTR_variant	Exon 81 of 81	ENST00000389840.7	NP_775899.3
PGS1	NM_024419.5	c.*11-158G>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	c.*3C>T		3_prime_UTR_variant	Exon 81 of 81	5	NM_173628.4	ENSP00000374490.6
PGS1	ENST00000262764.11	c.*11-158G>A		intron_variant	Intron 9 of 9	1	NM_024419.5	ENSP00000262764.5

Frequencies

GnomAD3 genomes AF: 0.00509 AC: 775 AN: 152232 Hom.: 5 Cov.: 33

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.: 11 AF XY: 0.00583 AC XY: 790 AN XY: 135616

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.: 57 Cov.: 31 AF XY: 0.00645 AC XY: 4689 AN XY: 727004

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.: 5 Cov.: 33 AF XY: 0.00554 AC XY: 413 AN XY: 74500

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.: 1

Bravo AF: 0.00371

Asia WGS AF: 0.00115 AC: 5 AN: 3478

EpiCase AF: 0.00709

EpiControl AF: 0.00557

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PGS1-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). -

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

Other links and lift over

dbSNP: rs72914863; hg19: chr17-76419984;