4-2884566-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001354761.2(ADD1):c.410C>T(p.Ala137Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,612,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
ADD1
NM_001354761.2 missense
NM_001354761.2 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 7.71
Genes affected
ADD1 (HGNC:243): (adducin 1) Adducins are a family of cytoskeletal proteins encoded by three genes (alpha, beta, and gamma). Adducin acts as a heterodimer of the related alpha, beta, or gamma subunits. The protein encoded by this gene represents the alpha subunit. Alpha- and beta-adducin include a protease-resistant N-terminal region and a protease-sensitive, hydrophilic C-terminal region. Adducin binds with high affinity to Ca(2+)/calmodulin and is a substrate for protein kinases A and C. [provided by RefSeq, Aug 2017]
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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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADD1 | NM_001354761.2 | c.410C>T | p.Ala137Val | missense_variant | 4/16 | ENST00000683351.1 | NP_001341690.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADD1 | ENST00000683351.1 | c.410C>T | p.Ala137Val | missense_variant | 4/16 | NM_001354761.2 | ENSP00000508142.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152112Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460750Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 726624
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152112Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74290
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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 | Mar 02, 2023 | The c.410C>T (p.A137V) alteration is located in exon 4 (coding exon 3) of the ADD1 gene. This alteration results from a C to T substitution at nucleotide position 410, causing the alanine (A) at amino acid position 137 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;.;T;.;T;T;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;.;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;.;.;.;L;L;L
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D;D;D;D
Sift4G
Benign
T;T;T;D;T;T;T;T;T
Polyphen
B;.;.;.;.;P;.;.;P
Vest4
MutPred
Gain of glycosylation at S133 (P = 0.043);Gain of glycosylation at S133 (P = 0.043);Gain of glycosylation at S133 (P = 0.043);Gain of glycosylation at S133 (P = 0.043);Gain of glycosylation at S133 (P = 0.043);Gain of glycosylation at S133 (P = 0.043);Gain of glycosylation at S133 (P = 0.043);Gain of glycosylation at S133 (P = 0.043);Gain of glycosylation at S133 (P = 0.043);
MVP
MPC
ClinPred
D
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