chr17-78204885-G-C

Variant names:

• chr17-78204885-G-C
• rs1008777397
• NM_001010982.5:c.452G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001010982.5(AFMID):​c.452G>C​(p.Arg151Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. R151Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AFMID NM_001010982.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35396263).

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.452G>C	p.Arg151Pro	missense	Exon 6 of 11	NP_001010982.2	Q63HM1-1
	AFMID	NM_001145526.3		c.452G>C	p.Arg151Pro	missense	Exon 6 of 11	NP_001138998.1	Q63HM1-2
	AFMID	NM_001391999.1		c.452G>C	p.Arg151Pro	missense	Exon 6 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.452G>C	p.Arg151Pro	missense	Exon 6 of 11	ENSP00000386890.4	Q63HM1-1
	AFMID	ENST00000327898.9	TSL:1	c.452G>C	p.Arg151Pro	missense	Exon 6 of 11	ENSP00000328938.5	Q63HM1-2
	AFMID	ENST00000857474.1		c.545G>C	p.Arg182Pro	missense	Exon 7 of 12	ENSP00000527533.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	9.3
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		-0.13
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.30
Sift	Benign	0.031	D
Sift4G	Benign	0.090	T
Polyphen		0.99	D
Vest4		0.51
MutPred		0.58		Loss of MoRF binding (P = 0.0172)
MVP		0.23
MPC		0.87
ClinPred		0.95	D
GERP RS		-6.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.77
gMVP		0.81
Mutation Taster		=76/24	polymorphism

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: rs1008777397; hg19: chr17-76200966;