chr17-78424312-G-A

Variant names:

• chr17-78424312-G-A
• rs55973973
• NM_024419.5:c.*262G>A

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.*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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.663
• Publications: 9 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=-0.83).
• BP6: Variant 17-78424312-G-A is Benign according to our data. Variant chr17-78424312-G-A is described in ClinVar as Benign. ClinVar VariationId is 1269355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 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.*262G>A		3_prime_UTR	Exon 10 of 10	NP_077733.3
	DNAH17	NM_173628.4	MANE Select	c.13142-159C>T		intron	N/A	NP_775899.3	Q9UFH2-1
	PGS1	NR_110601.2		n.1799G>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.*262G>A		3_prime_UTR	Exon 10 of 10	ENSP00000262764.5	Q32NB8-1
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.13142-159C>T		intron	N/A	ENSP00000374490.6	Q9UFH2-1
	PGS1	ENST00000588281.5	TSL:1	n.1531G>A		non_coding_transcript_exon	Exon 6 of 6

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

African (AFR) AF: 0.178 AC: 3045 AN: 17152

American (AMR) AF: 0.109 AC: 2045 AN: 18806

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 3475 AN: 15128

East Asian (EAS) AF: 0.0204 AC: 654 AN: 32008

South Asian (SAS) AF: 0.166 AC: 8229 AN: 49564

European-Finnish (FIN) AF: 0.114 AC: 3330 AN: 29166

Middle Eastern (MID) AF: 0.208 AC: 511 AN: 2454

European-Non Finnish (NFE) AF: 0.176 AC: 89096 AN: 507268

Other (OTH) AF: 0.162 AC: 5576 AN: 34316

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

African (AFR) AF: 0.171 AC: 7106 AN: 41544

American (AMR) AF: 0.124 AC: 1896 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 788 AN: 3472

East Asian (EAS) AF: 0.0306 AC: 158 AN: 5168

South Asian (SAS) AF: 0.154 AC: 744 AN: 4830

European-Finnish (FIN) AF: 0.113 AC: 1196 AN: 10612

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11353 AN: 68006

Other (OTH) AF: 0.162 AC: 342 AN: 2114

Alfa AF: 0.169 Hom.: 457

Bravo AF: 0.159

Asia WGS AF: 0.0740 AC: 260 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	-0.83
CADD	Benign	1.3
DANN	Benign	0.54
PhyloP100		-0.66
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: rs55973973; hg19: chr17-76420393; COSMIC: COSV105011834; COSMIC: COSV105011834;