chr17-78205145-C-T

Variant names:

• chr17-78205145-C-T
• rs200064003
• NM_001010982.5:c.520C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30157423).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010982.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFMID	NM_001010982.5	MANE Select	c.520C>T	p.Leu174Phe	missense	Exon 7 of 11	NP_001010982.2	Q63HM1-1
	AFMID	NM_001145526.3		c.520C>T	p.Leu174Phe	missense	Exon 7 of 11	NP_001138998.1	Q63HM1-2
	AFMID	NM_001391999.1		c.520C>T	p.Leu174Phe	missense	Exon 7 of 10	NP_001378928.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFMID	ENST00000409257.10	TSL:1 MANE Select	c.520C>T	p.Leu174Phe	missense	Exon 7 of 11	ENSP00000386890.4	Q63HM1-1
	AFMID	ENST00000327898.9	TSL:1	c.520C>T	p.Leu174Phe	missense	Exon 7 of 11	ENSP00000328938.5	Q63HM1-2
	AFMID	ENST00000857474.1		c.613C>T	p.Leu205Phe	missense	Exon 8 of 12	ENSP00000527533.1

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152248 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.0000888 AC: 22 AN: 247712 AF XY: 0.0000746

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 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.: 0 Cov.: 31 AF XY: 0.000118 AC XY: 86 AN XY: 726554

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.0000898 AC: 4 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26062

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 85980

European-Finnish (FIN) AF: 0.0000563 AC: 3 AN: 53314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000131 AC: 146 AN: 1111596

Other (OTH) AF: 0.0000497 AC: 3 AN: 60312

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152366 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74510

African (AFR) AF: 0.0000240 AC: 1 AN: 41602

American (AMR) AF: 0.0000654 AC: 1 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68036

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000234 Hom.: 0

Bravo AF: 0.000155

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000115 AC: 14

EpiCase AF: 0.000109

EpiControl AF: 0.0000594

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		1.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.27
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.36
MVP		0.53
MPC		0.29
ClinPred		0.51	D
GERP RS		5.3
Varity_R		0.72
gMVP		0.76
Mutation Taster		=37/63	disease causing

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

Other links and lift over

dbSNP: rs200064003; hg19: chr17-76201226;