17-78423801-G-A

Variant names:

• chr17-78423801-G-A
• rs72903323
• NM_173628.4:c.*105C>T

Variant summary

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

The NM_173628.4(DNAH17):​c.*105C>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 0.161 in 1,449,870 control chromosomes in the GnomAD database, including 19,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (1985 hom., cov: 32)
  • Exomes 𝑓: 0.16 (17918 hom.)
• Consequence: DNAH17 NM_173628.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.284
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-78423801-G-A is Benign according to our data. Variant chr17-78423801-G-A is described in ClinVar as Benign. ClinVar VariationId is 1246795.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_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.*105C>T		3_prime_UTR	Exon 81 of 81	NP_775899.3	Q9UFH2-1
	PGS1	NM_024419.5	MANE Select	c.*11-260G>A		intron	N/A	NP_077733.3
	PGS1	NR_110601.2		n.1548-260G>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.*105C>T		3_prime_UTR	Exon 81 of 81	ENSP00000374490.6	Q9UFH2-1
	PGS1	ENST00000262764.11	TSL:1 MANE Select	c.*11-260G>A		intron	N/A	ENSP00000262764.5	Q32NB8-1
	PGS1	ENST00000588281.5	TSL:1	n.1280-260G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23761 AN: 152030 Hom.: 1982 Cov.: 32

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: 0.153

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.162 AC: 209952 AN: 1297722 Hom.: 17918 Cov.: 19 AF XY: 0.162 AC XY: 103816 AN XY: 642298

African (AFR) AF: 0.174 AC: 5139 AN: 29520

American (AMR) AF: 0.0909 AC: 3169 AN: 34850

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 4725 AN: 20812

East Asian (EAS) AF: 0.0217 AC: 837 AN: 38542

South Asian (SAS) AF: 0.162 AC: 11725 AN: 72542

European-Finnish (FIN) AF: 0.113 AC: 4999 AN: 44300

Middle Eastern (MID) AF: 0.202 AC: 923 AN: 4578

European-Non Finnish (NFE) AF: 0.170 AC: 169849 AN: 998324

Other (OTH) AF: 0.158 AC: 8586 AN: 54254

GnomAD4 genome AF: 0.156 AC: 23781 AN: 152148 Hom.: 1985 Cov.: 32 AF XY: 0.152 AC XY: 11279 AN XY: 74396

African (AFR) AF: 0.171 AC: 7103 AN: 41496

American (AMR) AF: 0.124 AC: 1898 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 789 AN: 3470

East Asian (EAS) AF: 0.0306 AC: 159 AN: 5190

South Asian (SAS) AF: 0.153 AC: 738 AN: 4818

European-Finnish (FIN) AF: 0.112 AC: 1184 AN: 10586

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

European-Non Finnish (NFE) AF: 0.167 AC: 11358 AN: 67988

Other (OTH) AF: 0.162 AC: 342 AN: 2110

Alfa AF: 0.160 Hom.: 609

Bravo AF: 0.159

Asia WGS AF: 0.0770 AC: 270 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	-0.90
CADD	Benign	0.46
DANN	Benign	0.77
PhyloP100		-0.28
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: rs72903323; hg19: chr17-76419882;