17-78424292-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024419.5(PGS1):​c.*242G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PGS1 NM_024419.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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>T		3_prime_UTR	Exon 10 of 10	NP_077733.3
	DNAH17	NM_173628.4	MANE Select	c.13142-139C>A		intron	N/A	NP_775899.3	Q9UFH2-1
	PGS1	NR_110601.2		n.1779G>T		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>T		3_prime_UTR	Exon 10 of 10	ENSP00000262764.5	Q32NB8-1
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.13142-139C>A		intron	N/A	ENSP00000374490.6	Q9UFH2-1
	PGS1	ENST00000588281.5	TSL:1	n.1511G>T		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 950242 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 471668

African (AFR) AF: 0.00 AC: 0 AN: 21694

American (AMR) AF: 0.00 AC: 0 AN: 19508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16694

East Asian (EAS) AF: 0.00 AC: 0 AN: 33276

South Asian (SAS) AF: 0.00 AC: 0 AN: 55714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2906

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 728418

Other (OTH) AF: 0.00 AC: 0 AN: 42306

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.60
PhyloP100		-0.29

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;