17-78191028-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001010982.5(AFMID):​c.122C>A​(p.Ala41Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000068 ( 0 hom. )

Consequence

AFMID
NM_001010982.5 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.778
Variant links:
Genes affected
AFMID (HGNC:20910): (arylformamidase) Predicted to enable hydrolase activity. Predicted to be involved in tryptophan catabolic process to kynurenine. Predicted to be located in cytosol and nucleus. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33420372).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AFMIDNM_001010982.5 linkc.122C>A p.Ala41Asp missense_variant Exon 2 of 11 ENST00000409257.10 NP_001010982.2 Q63HM1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AFMIDENST00000409257.10 linkc.122C>A p.Ala41Asp missense_variant Exon 2 of 11 1 NM_001010982.5 ENSP00000386890.4 Q63HM1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251232
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135828
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00000880
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461816
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727198
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000447
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:
0.00000360
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000312
Hom.:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.122C>A (p.A41D) alteration is located in exon 2 (coding exon 2) of the AFMID gene. This alteration results from a C to A substitution at nucleotide position 122, causing the alanine (A) at amino acid position 41 to be replaced by an aspartic acid (D). 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
Uncertain
0.47
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.18
T;T;T;T;T;.;T;T
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.44
FATHMM_MKL
Benign
0.59
D
LIST_S2
Benign
0.80
T;T;T;T;T;T;T;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.33
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
L;.;.;.;.;L;.;.
PrimateAI
Benign
0.32
T
PROVEAN
Uncertain
-2.7
D;.;.;.;.;D;.;.
REVEL
Benign
0.063
Sift
Uncertain
0.0060
D;.;.;.;.;D;.;.
Sift4G
Uncertain
0.0060
D;D;D;D;D;D;D;T
Polyphen
0.84
P;.;.;.;.;P;.;.
Vest4
0.39
MutPred
0.62
Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);.;
MVP
0.49
MPC
0.57
ClinPred
0.82
D
GERP RS
1.3
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
2.1
Varity_R
0.22
gMVP
0.83

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: rs758457659; hg19: chr17-76187109; API