11-34896828-A-T

Variant names:

• chr11-34896828-A-T
• rs2986429
• NM_015957.4:c.58-1718T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015957.4(APIP):​c.58-1718T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: APIP NM_015957.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• Publications: 22 publications found

Genes affected

APIP (HGNC:17581): (APAF1 interacting protein) Enables identical protein binding activity; methylthioribulose 1-phosphate dehydratase activity; and zinc ion binding activity. Involved in several processes, including L-methionine salvage from methylthioadenosine; protein homotetramerization; and pyroptosis. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015957.4. 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
	APIP	NM_015957.4	MANE Select	c.58-1718T>A		intron	N/A	NP_057041.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APIP	ENST00000395787.4	TSL:1 MANE Select	c.58-1718T>A		intron	N/A	ENSP00000379133.3
	APIP	ENST00000965076.1		c.85T>A	p.Phe29Ile	missense	Exon 2 of 7	ENSP00000635135.1
	APIP	ENST00000901543.1		c.58-1718T>A		intron	N/A	ENSP00000571602.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1134266 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 556556

African (AFR) AF: 0.00 AC: 0 AN: 24366

American (AMR) AF: 0.00 AC: 0 AN: 28262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15922

East Asian (EAS) AF: 0.00 AC: 0 AN: 12830

South Asian (SAS) AF: 0.00 AC: 0 AN: 76136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12640

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4398

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 918286

Other (OTH) AF: 0.00 AC: 0 AN: 41426

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	15
DANN	Benign	0.85
PhyloP100		-0.089

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.24		Position offset: 27

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

Other links and lift over

dbSNP: rs2986429; hg19: chr11-34918375;