17-78205154-G-T

Variant names:

• chr17-78205154-G-T
• rs202188832
• NM_001010982.5:c.529G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001010982.5(AFMID):​c.529G>T​(p.Asp177Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,460,558 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D177N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: AFMID NM_001010982.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.723
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.529G>T	p.Asp177Tyr	missense	Exon 7 of 11	NP_001010982.2	Q63HM1-1
	AFMID	NM_001145526.3		c.529G>T	p.Asp177Tyr	missense	Exon 7 of 11	NP_001138998.1	Q63HM1-2
	AFMID	NM_001391999.1		c.529G>T	p.Asp177Tyr	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.529G>T	p.Asp177Tyr	missense	Exon 7 of 11	ENSP00000386890.4	Q63HM1-1
	AFMID	ENST00000327898.9	TSL:1	c.529G>T	p.Asp177Tyr	missense	Exon 7 of 11	ENSP00000328938.5	Q63HM1-2
	AFMID	ENST00000857474.1		c.622G>T	p.Asp208Tyr	missense	Exon 8 of 12	ENSP00000527533.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000822 AC: 12 AN: 1460558 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 726438

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 85934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53276

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

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111526

Other (OTH) AF: 0.00 AC: 0 AN: 60314

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.95
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.72
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.98	D
Vest4		0.60
MutPred		0.55		Gain of ubiquitination at K180 (P = 0.0741)
MVP		0.18
MPC		0.71
ClinPred		0.94	D
GERP RS		-10
Varity_R		0.60
gMVP		0.81
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs202188832; hg19: chr17-76201235;