rs758457659

Variant names:

• chr17-78191028-C-A
• rs758457659
• NM_001010982.5:c.122C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-78191028-C-A
• chr17-78191028-C-T

Variant summary

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

The NM_001010982.5(AFMID):​c.122C>A​(p.Ala41Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: AFMID NM_001010982.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.778
• 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=0.33420372).

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.122C>A	p.Ala41Asp	missense	Exon 2 of 11	NP_001010982.2	Q63HM1-1
	AFMID	NM_001145526.3		c.122C>A	p.Ala41Asp	missense	Exon 2 of 11	NP_001138998.1	Q63HM1-2
	AFMID	NM_001391999.1		c.122C>A	p.Ala41Asp	missense	Exon 2 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.122C>A	p.Ala41Asp	missense	Exon 2 of 11	ENSP00000386890.4	Q63HM1-1
	AFMID	ENST00000327898.9	TSL:1	c.122C>A	p.Ala41Asp	missense	Exon 2 of 11	ENSP00000328938.5	Q63HM1-2
	AFMID	ENST00000589256.5	TSL:1	c.122C>A	p.Ala41Asp	missense	Exon 2 of 3	ENSP00000466859.1	W4VSQ7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251232 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461816 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727198

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111980

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ExAC AF: 0.0000165 AC: 2

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	Uncertain	0.47
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.78
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.063
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.84	P
Vest4		0.39
MutPred		0.62		Loss of helix (P = 0.0167)
MVP		0.49
MPC		0.57
ClinPred		0.82	D
GERP RS		1.3
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.1
Varity_R		0.22
gMVP		0.83
Mutation Taster		=89/11	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: rs758457659; hg19: chr17-76187109;