NM_015375.3:c.86G>A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_015375.3(DSTYK):c.86G>A(p.Arg29Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000658 in 1,599,294 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_015375.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000723 AC: 110AN: 152224Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00101 AC: 223AN: 220688Hom.: 0 AF XY: 0.00123 AC XY: 149AN XY: 121330
GnomAD4 exome AF: 0.000651 AC: 942AN: 1446952Hom.: 2 Cov.: 32 AF XY: 0.000732 AC XY: 527AN XY: 719528
GnomAD4 genome AF: 0.000722 AC: 110AN: 152342Hom.: 0 Cov.: 33 AF XY: 0.000805 AC XY: 60AN XY: 74498
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
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The DSTYK p.Arg29Gln variant was identified in 3 of 622 proband chromosomes (frequency: 0.0048) from individuals with congenital abnormalities of the kidney and urinary tract and was not identified in 768 control chromosomes from healthy individuals (Sanna-Cherchi_2013_PMID:23862974). The variant was identified in dbSNP (ID: rs200780796) and ClinVar (classified as likely benign by Invitae and benign by Mendelics). The variant was identified in control databases in 228 of 252060 chromosomes at a frequency of 0.0009045 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Ashkenazi Jewish in 75 of 9706 chromosomes (freq: 0.007727), South Asian in 54 of 28984 chromosomes (freq: 0.001863), European (non-Finnish) in 75 of 114366 chromosomes (freq: 0.000656), Other in 4 of 6568 chromosomes (freq: 0.000609), Latino in 19 of 33852 chromosomes (freq: 0.000561) and African in 1 of 22128 chromosomes (freq: 0.000045), but was not observed in the East Asian or European (Finnish) populations. The p.Arg29 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -
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Congenital anomalies of kidney and urinary tract 1 Pathogenic:1Benign:1
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not specified Uncertain:1Benign:1
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Variant summary: RIPK5 (also known as DSTYK) c.86G>A (p.Arg29Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0009 in 252060 control chromosomes (gnomAD), predominantly at a frequency of 0.0019 within the South Asian subpopulation in the gnomAD database. c.86G>A has been reported in the literature in individuals affected with congenital abnormalities of the kidney and urinary tract (Sanna-Cherchi_2013). This report does not provide unequivocal conclusions about association of the variant with RIPK5-Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters have assessed the variant since 2014: one classified the variant as uncertain significance, two as likely benign, and one as benign. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at