rs16835896
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2
The NM_001388419.1(KALRN):āc.8918A>Gā(p.Asn2973Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000317 in 1,614,072 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.00041 ( 1 hom., cov: 33)
Exomes š: 0.00031 ( 5 hom. )
Consequence
KALRN
NM_001388419.1 missense
NM_001388419.1 missense
Scores
1
16
Clinical Significance
Conservation
PhyloP100: 3.73
Genes affected
KALRN (HGNC:4814): (kalirin RhoGEF kinase) Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein that interacts with the huntingtin-associated protein 1, which is a huntingtin binding protein that may function in vesicle trafficking. [provided by RefSeq, Apr 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, KALRN
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0054593384).
BP6
?
Variant 3-124719427-A-G is Benign according to our data. Variant chr3-124719427-A-G is described in ClinVar as [Benign]. Clinvar id is 3033114.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd4 at 63 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KALRN | NM_001388419.1 | c.8918A>G | p.Asn2973Ser | missense_variant | 60/60 | ENST00000682506.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KALRN | ENST00000682506.1 | c.8918A>G | p.Asn2973Ser | missense_variant | 60/60 | NM_001388419.1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000414 AC: 63AN: 152176Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000981 AC: 245AN: 249856Hom.: 3 AF XY: 0.000936 AC XY: 127AN XY: 135618
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GnomAD4 exome AF: 0.000306 AC: 448AN: 1461778Hom.: 5 Cov.: 31 AF XY: 0.000344 AC XY: 250AN XY: 727196
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GnomAD4 genome ? AF: 0.000414 AC: 63AN: 152294Hom.: 1 Cov.: 33 AF XY: 0.000483 AC XY: 36AN XY: 74478
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
KALRN-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 19, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Vest4
MVP
ClinPred
T
GERP RS
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at