chr5-140537517-C-G
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2
The NM_017747.3(ANKHD1):c.7156C>G(p.Pro2386Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000688 in 1,613,472 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0034 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00041 ( 6 hom. )
Consequence
ANKHD1
NM_017747.3 missense
NM_017747.3 missense
Scores
6
8
Clinical Significance
Conservation
PhyloP100: 2.91
Genes affected
ANKHD1 (HGNC:24714): (ankyrin repeat and KH domain containing 1) This gene encodes a protein with multiple ankyrin repeat domains and a single KH-domain. The protein is thought to function as a scaffolding protein, and it may be involved in the regulation of caspases and thereby play an antiapoptotic role in cell survival. Alternative splicing results in multiple transcript variants, one of which generates a fusion transcript (MASK-BP3) with the downstream eIF4E-binding protein 3 (EIF4EBP3) gene, resulting in a protein comprised of the ANKHD1 sequence for the majority of the protein and a different C-terminus due to an alternate reading frame for the EIF4EBP3 segments. [provided by RefSeq, Sep 2010]
SRA1 (HGNC:11281): (steroid receptor RNA activator 1) Both long non-coding and protein-coding RNAs are transcribed from this gene, and they represent alternatively spliced transcript variants. This gene was initially defined as a non-coding RNA, which is a coactivator for several nuclear receptors (NRs) and is associated with breast cancer. It has now been found that this gene is involved in the regulation of many NR and non-NR activities, including metabolism, adipogenesis and chromatin organization. The long non-coding RNA transcripts interact with a variety of proteins, including the protein encoded by this gene. The encoded protein acts as a transcriptional repressor by binding to the non-coding RNA. [provided by RefSeq, Mar 2012]
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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, ANKHD1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0054234564).
BP6
?
Variant 5-140537517-C-G is Benign according to our data. Variant chr5-140537517-C-G is described in ClinVar as [Benign]. Clinvar id is 775225.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 509 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANKHD1 | NM_017747.3 | c.7156C>G | p.Pro2386Ala | missense_variant | 31/34 | ENST00000360839.7 | |
ANKHD1-EIF4EBP3 | NM_020690.6 | c.7156C>G | p.Pro2386Ala | missense_variant | 31/36 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANKHD1 | ENST00000360839.7 | c.7156C>G | p.Pro2386Ala | missense_variant | 31/34 | 1 | NM_017747.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00335 AC: 509AN: 152124Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000878 AC: 218AN: 248292Hom.: 2 AF XY: 0.000550 AC XY: 74AN XY: 134434
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GnomAD4 exome AF: 0.000410 AC: 599AN: 1461230Hom.: 6 Cov.: 30 AF XY: 0.000365 AC XY: 265AN XY: 726974
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GnomAD4 genome ? AF: 0.00336 AC: 511AN: 152242Hom.: 2 Cov.: 32 AF XY: 0.00340 AC XY: 253AN XY: 74446
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3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 05, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;N;N;N
PrimateAI
Uncertain
T
REVEL
Benign
Sift4G
Benign
T;T;T;T;T;T
Polyphen
0.82
.;P;.;.;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at