chr17-78424052-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000262764.11(PGS1):​c.*11-9G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000452 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00046 ( 0 hom. )

Consequence

PGS1
ENST00000262764.11 splice_polypyrimidine_tract, intron

Scores

4
3
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.67
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAH17NM_173628.4 linkuse as main transcriptc.13243C>T p.Arg4415Cys missense_variant 81/81 ENST00000389840.7 NP_775899.3
PGS1NM_024419.5 linkuse as main transcriptc.*11-9G>A splice_polypyrimidine_tract_variant, intron_variant ENST00000262764.11 NP_077733.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAH17ENST00000389840.7 linkuse as main transcriptc.13243C>T p.Arg4415Cys missense_variant 81/815 NM_173628.4 ENSP00000374490 P1Q9UFH2-1
PGS1ENST00000262764.11 linkuse as main transcriptc.*11-9G>A splice_polypyrimidine_tract_variant, intron_variant 1 NM_024419.5 ENSP00000262764 P1Q32NB8-1

Frequencies

GnomAD3 genomes
AF:
0.000342
AC:
52
AN:
152222
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000523
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000353
AC:
88
AN:
249486
Hom.:
0
AF XY:
0.000407
AC XY:
55
AN XY:
135002
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.000347
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000217
Gnomad SAS exome
AF:
0.000457
Gnomad FIN exome
AF:
0.000231
Gnomad NFE exome
AF:
0.000420
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000463
AC:
677
AN:
1461706
Hom.:
0
Cov.:
31
AF XY:
0.000474
AC XY:
345
AN XY:
727134
show subpopulations
Gnomad4 AFR exome
AF:
0.000568
Gnomad4 AMR exome
AF:
0.000425
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.000441
Gnomad4 FIN exome
AF:
0.000169
Gnomad4 NFE exome
AF:
0.000500
Gnomad4 OTH exome
AF:
0.000464
GnomAD4 genome
AF:
0.000341
AC:
52
AN:
152340
Hom.:
0
Cov.:
33
AF XY:
0.000362
AC XY:
27
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.000523
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000377
Hom.:
0
Bravo
AF:
0.000340
TwinsUK
AF:
0.00108
AC:
4
ALSPAC
AF:
0.00104
AC:
4
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000436
AC:
53
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000709
EpiControl
AF:
0.000711

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 18, 2021The c.13243C>T (p.R4415C) alteration is located in exon 81 (coding exon 80) of the DNAH17 gene. This alteration results from a C to T substitution at nucleotide position 13243, causing the arginine (R) at amino acid position 4415 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.63
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.34
CADD
Pathogenic
31
DANN
Pathogenic
1.0
Eigen
Pathogenic
0.80
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.0079
T
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-0.86
T
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.58
T
REVEL
Benign
0.25
Vest4
0.38
MVP
0.53
ClinPred
0.41
T
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.13
gMVP
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.81
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.81
Position offset: 2
DS_AL_spliceai
0.46
Position offset: 9

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs142983650; hg19: chr17-76420133; API