11-77842600-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024684.4(AAMDC):​c.104C>T​(p.Thr35Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

AAMDC
NM_024684.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18
Variant links:
Genes affected
AAMDC (HGNC:30205): (adipogenesis associated Mth938 domain containing) Predicted to be involved in positive regulation of fat cell differentiation. Predicted to act upstream of or within negative regulation of apoptotic process and positive regulation of transcription by RNA polymerase II. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
RSF1 (HGNC:18118): (remodeling and spacing factor 1) This gene encodes a nuclear protein that interacts with hepatitis B virus X protein (HBX) and facilitates transcription of hepatitis B virus genes by the HBX transcription activator, suggesting a role for this interaction in the virus life cycle. This protein also interacts with SNF2H protein to form the RSF chromatin-remodeling complex, where the SNF2H subunit functions as the nucleosome-dependent ATPase, and this protein as the histone chaperone. [provided by RefSeq, Sep 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25558943).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AAMDCNM_024684.4 linkc.104C>T p.Thr35Ile missense_variant Exon 2 of 4 ENST00000393427.7 NP_078960.1 Q9H7C9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AAMDCENST00000393427.7 linkc.104C>T p.Thr35Ile missense_variant Exon 2 of 4 1 NM_024684.4 ENSP00000377078.2 Q9H7C9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251006
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135660
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000441
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461660
Hom.:
0
Cov.:
32
AF XY:
0.0000138
AC XY:
10
AN XY:
727136
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000624
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 27, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.104C>T (p.T35I) alteration is located in exon 2 (coding exon 1) of the AAMDC gene. This alteration results from a C to T substitution at nucleotide position 104, causing the threonine (T) at amino acid position 35 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
.;T;T;.;.;.;T;T;T
Eigen
Benign
-0.12
Eigen_PC
Benign
0.0018
FATHMM_MKL
Benign
0.72
D
LIST_S2
Benign
0.75
T;.;T;T;.;T;T;T;T
M_CAP
Benign
0.0064
T
MetaRNN
Benign
0.26
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;L;L;.;.;.;.;.;.
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-2.0
N;N;N;N;N;.;N;N;N
REVEL
Benign
0.031
Sift
Benign
0.076
T;T;T;D;D;.;T;T;T
Sift4G
Benign
0.13
T;T;T;T;D;D;T;D;T
Polyphen
0.14
B;B;B;P;.;.;.;.;.
Vest4
0.088
MutPred
0.35
Loss of disorder (P = 0.0323);Loss of disorder (P = 0.0323);Loss of disorder (P = 0.0323);Loss of disorder (P = 0.0323);Loss of disorder (P = 0.0323);Loss of disorder (P = 0.0323);Loss of disorder (P = 0.0323);Loss of disorder (P = 0.0323);.;
MVP
0.35
MPC
0.024
ClinPred
0.36
T
GERP RS
2.7
Varity_R
0.20
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs755877540; hg19: chr11-77553646; API