17-78424312-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024419.5(PGS1):c.*262G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 858,100 control chromosomes in the GnomAD database, including 11,878 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (1981 hom., cov: 33)
  • Exomes 𝑓: 0.16 (9897 hom.)
• Consequence: PGS1 NM_024419.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.663

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-78424312-G-A is Benign according to our data. Variant chr17-78424312-G-A is described in ClinVar as [Benign]. Clinvar id is 1269355.Status of the report is criteria_provided_single_submitter, 1 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	UniProt
PGS1	NM_024419.5	c.*262G>A		3_prime_UTR_variant	10/10	ENST00000262764.11
DNAH17	NM_173628.4	c.13142-159C>T		intron_variant		ENST00000389840.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGS1	ENST00000262764.11	c.*262G>A		3_prime_UTR_variant	10/10	1	NM_024419.5	P1
DNAH17	ENST00000389840.7	c.13142-159C>T		intron_variant		5	NM_173628.4	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23775 AN: 152120 Hom.: 1979 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0307

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.164 AC: 115961 AN: 705862 Hom.: 9897 Cov.: 9 AF XY: 0.165 AC XY: 58748 AN XY: 357064

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.0204

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.176

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.156 AC: 23793 AN: 152238 Hom.: 1981 Cov.: 33 AF XY: 0.152 AC XY: 11283 AN XY: 74422

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.0306

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.162

Alfa AF: 0.169 Hom.: 457

Bravo AF: 0.159

Asia WGS AF: 0.0740 AC: 260 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.3
Dann	Benign	0.54

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: rs55973973; hg19: chr17-76420393; COSMIC: COSV105011834; COSMIC: COSV105011834;