17-78202576-A-G

Variant names:

• chr17-78202576-A-G
• rs1175716836
• NM_001010982.5:c.232A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001010982.5(AFMID):​c.232A>G​(p.Ile78Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: AFMID NM_001010982.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.676

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17190403).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFMID	NM_001010982.5	c.232A>G	p.Ile78Val	missense_variant	Exon 3 of 11	ENST00000409257.10	NP_001010982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFMID	ENST00000409257.10	c.232A>G	p.Ile78Val	missense_variant	Exon 3 of 11	1	NM_001010982.5	ENSP00000386890.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250760 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135616

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461446 Hom.: 0 Cov.: 34 AF XY: 0.00000688 AC XY: 5 AN XY: 727006

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000989

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.232A>G (p.I78V) alteration is located in exon 3 (coding exon 3) of the AFMID gene. This alteration results from a A to G substitution at nucleotide position 232, causing the isoleucine (I) at amino acid position 78 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	4.7
DANN	Benign	0.67
DEOGEN2	Benign	0.082	T;T;.;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.66	T;T;T;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.;L;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.70	N;.;N;.
REVEL	Benign	0.024
Sift	Benign	0.20	T;.;T;.
Sift4G	Benign	0.33	T;T;T;T
Polyphen		0.043	B;.;B;.
Vest4		0.15
MutPred		0.47		Loss of methylation at K75 (P = 0.1016);Loss of methylation at K75 (P = 0.1016);Loss of methylation at K75 (P = 0.1016);Loss of methylation at K75 (P = 0.1016);
MVP		0.55
MPC		0.20
ClinPred		0.058	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.025
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1175716836; hg19: chr17-76198657;