17-78191028-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 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

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33420372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFMID	NM_001010982.5	c.122C>A	p.Ala41Asp	missense_variant	Exon 2 of 11	ENST00000409257.10	NP_001010982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFMID	ENST00000409257.10	c.122C>A	p.Ala41Asp	missense_variant	Exon 2 of 11	1	NM_001010982.5	ENSP00000386890.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251232 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135828

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 SAS 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

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.0000447

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: 0.00000360

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.122C>A (p.A41D) alteration is located in exon 2 (coding exon 2) of the AFMID gene. This alteration results from a C to A substitution at nucleotide position 122, causing the alanine (A) at amino acid position 41 to be replaced by an aspartic acid (D). 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	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;T;T;T;T;.;T;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.80	T;T;T;T;T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.33	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.;.;.;.;L;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.7	D;.;.;.;.;D;.;.
REVEL	Benign	0.063
Sift	Uncertain	0.0060	D;.;.;.;.;D;.;.
Sift4G	Uncertain	0.0060	D;D;D;D;D;D;D;T
Polyphen		0.84	P;.;.;.;.;P;.;.
Vest4		0.39
MutPred		0.62		Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs758457659; hg19: chr17-76187109;