17-78191010-G-A

Variant names:

• chr17-78191010-G-A
• rs138405849
• NM_001010982.5:c.104G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001010982.5(AFMID):​c.104G>A​(p.Arg35Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000283 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (0 hom.)
• Consequence: AFMID NM_001010982.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.19
• Publications: 2 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12958384).

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.104G>A	p.Arg35Gln	missense	Exon 2 of 11	NP_001010982.2	Q63HM1-1
	AFMID	NM_001145526.3		c.104G>A	p.Arg35Gln	missense	Exon 2 of 11	NP_001138998.1	Q63HM1-2
	AFMID	NM_001391999.1		c.104G>A	p.Arg35Gln	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.104G>A	p.Arg35Gln	missense	Exon 2 of 11	ENSP00000386890.4	Q63HM1-1
	AFMID	ENST00000327898.9	TSL:1	c.104G>A	p.Arg35Gln	missense	Exon 2 of 11	ENSP00000328938.5	Q63HM1-2
	AFMID	ENST00000589256.5	TSL:1	c.104G>A	p.Arg35Gln	missense	Exon 2 of 3	ENSP00000466859.1	W4VSQ7

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152144 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

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: 0.000279

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000163 AC: 41 AN: 251242 AF XY: 0.000155

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000290

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000295 AC: 431 AN: 1461796 Hom.: 0 Cov.: 31 AF XY: 0.000297 AC XY: 216 AN XY: 727178

African (AFR) AF: 0.000239 AC: 8 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

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

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86230

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

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5746

European-Non Finnish (NFE) AF: 0.000363 AC: 404 AN: 1111986

Other (OTH) AF: 0.000149 AC: 9 AN: 60390

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152262 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74436

African (AFR) AF: 0.000120 AC: 5 AN: 41566

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.000322 Hom.: 0

Bravo AF: 0.000196

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000181 AC: 22

EpiCase AF: 0.000218

EpiControl AF: 0.000533

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	0.18
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.2
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.11
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.012	D
Polyphen		0.58	P
Vest4		0.34
MVP		0.46
MPC		0.33
ClinPred		0.066	T
GERP RS		2.8
Varity_R		0.049
gMVP		0.70
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs138405849; hg19: chr17-76187091; COSMIC: COSV100015078; COSMIC: COSV100015078;