chr20-10044490-G-C
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_022096.6(ANKEF1):āc.643G>Cā(p.Asp215His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 32)
Exomes š: 0.000017 ( 0 hom. )
Consequence
ANKEF1
NM_022096.6 missense
NM_022096.6 missense
Scores
11
4
4
Clinical Significance
Conservation
PhyloP100: 8.55
Genes affected
ANKEF1 (HGNC:15803): (ankyrin repeat and EF-hand domain containing 1) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.964
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ANKEF1 | NM_022096.6 | c.643G>C | p.Asp215His | missense_variant | 5/11 | ENST00000378392.6 | NP_071379.3 | |
SNAP25-AS1 | NR_040710.1 | n.500-17842C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ANKEF1 | ENST00000378392.6 | c.643G>C | p.Asp215His | missense_variant | 5/11 | 1 | NM_022096.6 | ENSP00000367644 | P1 | |
SNAP25-AS1 | ENST00000421143.6 | n.235-17842C>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152174Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251434Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135886
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461828Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727218
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74340
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 30, 2021 | The c.643G>C (p.D215H) alteration is located in exon 5 (coding exon 3) of the ANKEF1 gene. This alteration results from a G to C substitution at nucleotide position 643, causing the aspartic acid (D) at amino acid position 215 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
.;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Gain of disorder (P = 0.0904);Gain of disorder (P = 0.0904);
MVP
MPC
0.79
ClinPred
D
GERP RS
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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