chr6-34970074-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_015245.3(ANKS1A):āc.343T>Cā(p.Tyr115His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
ANKS1A
NM_015245.3 missense
NM_015245.3 missense
Scores
5
5
3
Clinical Significance
Conservation
PhyloP100: 8.02
Genes affected
ANKS1A (HGNC:20961): (ankyrin repeat and sterile alpha motif domain containing 1A) Predicted to enable ephrin receptor binding activity. Predicted to be involved in ephrin receptor signaling pathway; neuron remodeling; and substrate-dependent cell migration. Predicted to act upstream of or within negative regulation of ubiquitin-dependent protein catabolic process and regulation of ephrin receptor signaling pathway. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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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 | UniProt |
---|---|---|---|---|---|---|---|
ANKS1A | NM_015245.3 | c.343T>C | p.Tyr115His | missense_variant | 3/24 | ENST00000360359.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANKS1A | ENST00000360359.5 | c.343T>C | p.Tyr115His | missense_variant | 3/24 | 1 | NM_015245.3 | ||
ANKS1A | ENST00000649117.1 | c.343T>C | p.Tyr115His | missense_variant | 3/25 | P1 | |||
ANKS1A | ENST00000650178.1 | c.343T>C | p.Tyr115His | missense_variant | 3/10 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251336Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135854
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461854Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727226
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74360
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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 | Aug 10, 2023 | The c.343T>C (p.Y115H) alteration is located in exon 3 (coding exon 3) of the ANKS1A gene. This alteration results from a T to C substitution at nucleotide position 343, causing the tyrosine (Y) at amino acid position 115 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
Uncertain
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
Polyphen
1.0
.;D;.
Vest4
0.84
MutPred
Gain of disorder (P = 0.0375);Gain of disorder (P = 0.0375);Gain of disorder (P = 0.0375);
MVP
0.78
MPC
2.5
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