17-78205121-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001010982.5(AFMID):​c.496G>A​(p.Gly166Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,612,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

AFMID
NM_001010982.5 missense

Scores

15
2
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.88
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 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, 0.983

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AFMIDNM_001010982.5 linkc.496G>A p.Gly166Arg missense_variant Exon 7 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.496G>A p.Gly166Arg missense_variant Exon 7 of 11 1 NM_001010982.5 ENSP00000386890.4 Q63HM1-1

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000314
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000406
AC:
10
AN:
246392
Hom.:
0
AF XY:
0.0000225
AC XY:
3
AN XY:
133352
show subpopulations
Gnomad AFR exome
AF:
0.000192
Gnomad AMR exome
AF:
0.0000877
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000110
Gnomad SAS exome
AF:
0.0000332
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000895
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000158
AC:
23
AN:
1460150
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
726216
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.0000449
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000900
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152196
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.000314
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000161
Hom.:
0
Bravo
AF:
0.0000718
ExAC
AF:
0.0000412
AC:
5

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.496G>A (p.G166R) alteration is located in exon 7 (coding exon 7) of the AFMID gene. This alteration results from a G to A substitution at nucleotide position 496, causing the glycine (G) at amino acid position 166 to be replaced by an arginine (R). 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
Pathogenic
0.80
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Pathogenic
0.42
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.38
T;.
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.89
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Pathogenic
0.32
D
MetaRNN
Pathogenic
0.98
D;D
MetaSVM
Pathogenic
0.93
D
MutationAssessor
Pathogenic
4.5
H;H
PrimateAI
Uncertain
0.67
T
PROVEAN
Pathogenic
-7.4
D;D
REVEL
Pathogenic
0.91
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.99
MutPred
0.79
Gain of methylation at G166 (P = 0.0075);Gain of methylation at G166 (P = 0.0075);
MVP
0.98
MPC
0.86
ClinPred
1.0
D
GERP RS
5.3
Varity_R
0.97
gMVP
0.96

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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: rs770906558; hg19: chr17-76201202; API