rs72914863

Variant names:

• chr17-78423903-G-A
• rs72914863
• NM_173628.4:c.*3C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-78423903-G-A
• chr17-78423903-G-C
• chr17-78423903-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_173628.4(DNAH17):​c.*3C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00645 in 1,613,820 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0051 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0066 (57 hom.)
• Consequence: DNAH17 NM_173628.4 3_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.295
• Publications: 1 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-78423903-G-A is Benign according to our data. Variant chr17-78423903-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3033897.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00509 (775/152350) while in subpopulation NFE AF = 0.00717 (488/68022). AF 95% confidence interval is 0.00665. There are 5 homozygotes in GnomAd4. There are 413 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173628.4. 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
	DNAH17	NM_173628.4	MANE Select	c.*3C>T		3_prime_UTR	Exon 81 of 81	NP_775899.3	Q9UFH2-1
	PGS1	NM_024419.5	MANE Select	c.*11-158G>A		intron	N/A	NP_077733.3
	PGS1	NR_110601.2		n.1548-158G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.*3C>T		3_prime_UTR	Exon 81 of 81	ENSP00000374490.6	Q9UFH2-1
	PGS1	ENST00000262764.11	TSL:1 MANE Select	c.*11-158G>A		intron	N/A	ENSP00000262764.5	Q32NB8-1
	PGS1	ENST00000588281.5	TSL:1	n.1280-158G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00509 AC: 775 AN: 152232 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.0158

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00717

Gnomad OTH AF: 0.00384

GnomAD2 exomes AF: 0.00586 AC: 1470 AN: 250904 AF XY: 0.00583

Gnomad AFR exome AF: 0.00166

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.000435

Gnomad FIN exome AF: 0.0140

Gnomad NFE exome AF: 0.00859

Gnomad OTH exome AF: 0.00669

GnomAD4 exome AF: 0.00660 AC: 9642 AN: 1461470 Hom.: 57 Cov.: 31 AF XY: 0.00645 AC XY: 4689 AN XY: 727004

African (AFR) AF: 0.00152 AC: 51 AN: 33480

American (AMR) AF: 0.000850 AC: 38 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00126 AC: 33 AN: 26130

East Asian (EAS) AF: 0.000327 AC: 13 AN: 39698

South Asian (SAS) AF: 0.00254 AC: 219 AN: 86176

European-Finnish (FIN) AF: 0.0137 AC: 732 AN: 53336

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00742 AC: 8250 AN: 1111796

Other (OTH) AF: 0.00505 AC: 305 AN: 60366

GnomAD4 genome AF: 0.00509 AC: 775 AN: 152350 Hom.: 5 Cov.: 33 AF XY: 0.00554 AC XY: 413 AN XY: 74500

African (AFR) AF: 0.00190 AC: 79 AN: 41586

American (AMR) AF: 0.000980 AC: 15 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5192

South Asian (SAS) AF: 0.00248 AC: 12 AN: 4832

European-Finnish (FIN) AF: 0.0158 AC: 168 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00717 AC: 488 AN: 68022

Other (OTH) AF: 0.00380 AC: 8 AN: 2108

Alfa AF: 0.00576 Hom.: 1

Bravo AF: 0.00371

Asia WGS AF: 0.00115 AC: 5 AN: 3478

EpiCase AF: 0.00709

EpiControl AF: 0.00557

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PGS1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.77
DANN	Benign	0.59
PhyloP100		-0.29
Mutation Taster		=98/2	polymorphism

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: rs72914863; hg19: chr17-76419984;