Genetic Variant AFMID:p.Leu174Phe (chr17-78205145-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_001010982.5(AFMID):c.520C>T(p.Leu174Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,613,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

AFMID
NM_001010982.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.20

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]

AFMID links:

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=0.30157423).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFMID	NM_001010982.5 link	c.520C>T	p.Leu174Phe	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
AFMID	ENST00000409257.10 link	c.520C>T	p.Leu174Phe	missense_variant	Exon 7 of 11	1	NM_001010982.5	ENSP00000386890.4		Q63HM1-1

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000470

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000888

AC:

AN:

247712

Hom.:

AF XY:

0.0000746

AC XY:

AN XY:

134056

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000875

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000481

Gnomad NFE exome

AF:

0.000160

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000107

AC:

156

AN:

1460744

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

726554

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000898

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000563

Gnomad4 NFE exome

AF:

0.000131

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000230

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000470

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000255

Hom.:

Bravo

AF:

0.000155

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000594

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.520C>T (p.L174F) alteration is located in exon 7 (coding exon 7) of the AFMID gene. This alteration results from a C to T substitution at nucleotide position 520, causing the leucine (L) at amino acid position 174 to be replaced by a phenylalanine (F). 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

0.17

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;.

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Pathogenic

3.2

M;M

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.27

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

1.0

D;D

Vest4

0.36

MVP

0.53

MPC

0.29

ClinPred

0.51

GERP RS

5.3

Varity_R

0.72

gMVP

0.76

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over