11-128935600-C-T

Variant names:

• chr11-128935600-C-T
• rs570360865
• NM_022112.3:c.366G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_022112.3(TP53AIP1):​c.366G>A​(p.Arg122Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,419,018 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TP53AIP1 NM_022112.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 0 publications found

Genes affected

TP53AIP1 (HGNC:29984): (tumor protein p53 regulated apoptosis inducing protein 1) This gene is specifically expressed in the thymus, and encodes a protein that is localized to the mitochondrion. The expression of this gene is inducible by p53, and it is thought to play an important role in mediating p53-dependent apoptosis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022112.3. 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
	TP53AIP1	NM_022112.3	MANE Select	c.366G>A	p.Arg122Arg	synonymous	Exon 4 of 4	NP_071395.2	Q9HCN2-1
	TP53AIP1	NM_001195194.1		c.354G>A	p.Arg118Arg	synonymous	Exon 3 of 3	NP_001182123.1	Q9HCN2-4
	TP53AIP1	NM_001251964.2		c.*1892G>A		3_prime_UTR	Exon 2 of 2	NP_001238893.1	Q9HCN2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53AIP1	ENST00000531399.6	TSL:1 MANE Select	c.366G>A	p.Arg122Arg	synonymous	Exon 4 of 4	ENSP00000432743.1	Q9HCN2-1
	TP53AIP1	ENST00000530777.5	TSL:1	c.354G>A	p.Arg118Arg	synonymous	Exon 3 of 3	ENSP00000432908.1	Q9HCN2-4
	TP53AIP1	ENST00000602346.5	TSL:1	c.*1892G>A		3_prime_UTR	Exon 2 of 2	ENSP00000473353.1	Q9HCN2-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1419018 Hom.: 0 Cov.: 32 AF XY: 0.00000142 AC XY: 1 AN XY: 703594

African (AFR) AF: 0.00 AC: 0 AN: 32954

American (AMR) AF: 0.00 AC: 0 AN: 40668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25664

East Asian (EAS) AF: 0.00 AC: 0 AN: 38670

South Asian (SAS) AF: 0.00 AC: 0 AN: 81728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5324

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1098200

Other (OTH) AF: 0.00 AC: 0 AN: 59380

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.66
DANN	Benign	0.36
PhyloP100		-1.0

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: rs570360865; hg19: chr11-128805495;