rs12942703

Variant names:

• chr17-78424292-G-A
• rs12942703
• NM_024419.5:c.*242G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-78424292-G-A
• chr17-78424292-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024419.5(PGS1):​c.*242G>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 0.835 in 1,101,002 control chromosomes in the GnomAD database, including 385,741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52472 hom., cov: 33)
  • Exomes 𝑓: 0.84 (333269 hom.)
• Consequence: PGS1 NM_024419.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.292
• Publications: 11 publications found

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]

DNAH17 Gene-Disease associations (from GenCC):

• spermatogenic failure 39

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-78424292-G-A is Benign according to our data. Variant chr17-78424292-G-A is described in ClinVar as Benign. ClinVar VariationId is 1232395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024419.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGS1	NM_024419.5	MANE Select	c.*242G>A		3_prime_UTR	Exon 10 of 10	NP_077733.3
	DNAH17	NM_173628.4	MANE Select	c.13142-139C>T		intron	N/A	NP_775899.3	Q9UFH2-1
	PGS1	NR_110601.2		n.1779G>A		non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGS1	ENST00000262764.11	TSL:1 MANE Select	c.*242G>A		3_prime_UTR	Exon 10 of 10	ENSP00000262764.5	Q32NB8-1
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.13142-139C>T		intron	N/A	ENSP00000374490.6	Q9UFH2-1
	PGS1	ENST00000588281.5	TSL:1	n.1511G>A		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes AF: 0.828 AC: 126025 AN: 152148 Hom.: 52430 Cov.: 33

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.822

GnomAD4 exome AF: 0.837 AC: 793703 AN: 948736 Hom.: 333269 Cov.: 12 AF XY: 0.837 AC XY: 394071 AN XY: 470960

African (AFR) AF: 0.768 AC: 16627 AN: 21656

American (AMR) AF: 0.887 AC: 17306 AN: 19504

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 12849 AN: 16682

East Asian (EAS) AF: 0.979 AC: 32582 AN: 33274

South Asian (SAS) AF: 0.837 AC: 46564 AN: 55642

European-Finnish (FIN) AF: 0.886 AC: 26338 AN: 29712

Middle Eastern (MID) AF: 0.794 AC: 2302 AN: 2898

European-Non Finnish (NFE) AF: 0.830 AC: 603728 AN: 727114

Other (OTH) AF: 0.838 AC: 35407 AN: 42254

GnomAD4 genome AF: 0.828 AC: 126121 AN: 152266 Hom.: 52472 Cov.: 33 AF XY: 0.834 AC XY: 62058 AN XY: 74440

African (AFR) AF: 0.777 AC: 32288 AN: 41554

American (AMR) AF: 0.866 AC: 13249 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.773 AC: 2683 AN: 3472

East Asian (EAS) AF: 0.969 AC: 5006 AN: 5166

South Asian (SAS) AF: 0.846 AC: 4078 AN: 4820

European-Finnish (FIN) AF: 0.888 AC: 9425 AN: 10618

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.833 AC: 56656 AN: 68012

Other (OTH) AF: 0.824 AC: 1742 AN: 2114

Alfa AF: 0.826 Hom.: 64741

Bravo AF: 0.823

Asia WGS AF: 0.921 AC: 3201 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.52
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12942703; hg19: chr17-76420373;