NM_024419.5:c.*306T>A

Variant names:

• chr17-78424356-T-A
• rs56246296
• NM_024419.5:c.*306T>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.*306T>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 0.152 in 578,068 control chromosomes in the GnomAD database, including 7,400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (1977 hom., cov: 33)
  • Exomes 𝑓: 0.15 (5423 hom.)
• Consequence: PGS1 NM_024419.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.83
• 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=-0.88).
• BP6: Variant 17-78424356-T-A is Benign according to our data. Variant chr17-78424356-T-A is described in ClinVar as Benign. ClinVar VariationId is 1246188.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.*306T>A		3_prime_UTR	Exon 10 of 10	NP_077733.3
	DNAH17	NM_173628.4	MANE Select	c.13142-203A>T		intron	N/A	NP_775899.3	Q9UFH2-1
	PGS1	NR_110601.2		n.1843T>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.*306T>A		3_prime_UTR	Exon 10 of 10	ENSP00000262764.5	Q32NB8-1
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.13142-203A>T		intron	N/A	ENSP00000374490.6	Q9UFH2-1
	PGS1	ENST00000588281.5	TSL:1	n.1575T>A		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23754 AN: 152108 Hom.: 1974 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: 0.0308

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.150 AC: 63833 AN: 425842 Hom.: 5423 Cov.: 5 AF XY: 0.151 AC XY: 33213 AN XY: 219780

African (AFR) AF: 0.171 AC: 2123 AN: 12426

American (AMR) AF: 0.105 AC: 1686 AN: 16026

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 2745 AN: 12288

East Asian (EAS) AF: 0.0185 AC: 543 AN: 29298

South Asian (SAS) AF: 0.159 AC: 5102 AN: 32166

European-Finnish (FIN) AF: 0.113 AC: 2866 AN: 25434

Middle Eastern (MID) AF: 0.212 AC: 381 AN: 1800

European-Non Finnish (NFE) AF: 0.164 AC: 44611 AN: 272088

Other (OTH) AF: 0.155 AC: 3776 AN: 24316

GnomAD4 genome AF: 0.156 AC: 23774 AN: 152226 Hom.: 1977 Cov.: 33 AF XY: 0.152 AC XY: 11278 AN XY: 74430

African (AFR) AF: 0.171 AC: 7100 AN: 41522

American (AMR) AF: 0.124 AC: 1895 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 789 AN: 3472

East Asian (EAS) AF: 0.0307 AC: 159 AN: 5180

South Asian (SAS) AF: 0.154 AC: 741 AN: 4824

European-Finnish (FIN) AF: 0.112 AC: 1192 AN: 10614

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

European-Non Finnish (NFE) AF: 0.167 AC: 11346 AN: 68010

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

Alfa AF: 0.165 Hom.: 263

Bravo AF: 0.159

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

ClinVar submissions

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	-0.88
CADD	Benign	0.0090
DANN	Benign	0.71
PhyloP100		-1.8
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: rs56246296; hg19: chr17-76420437; COSMIC: COSV99428502; COSMIC: COSV99428502;