11-128936565-A-T

Variant names:

• chr11-128936565-A-T
• rs754039433
• NM_022112.3:c.226T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022112.3(TP53AIP1):​c.226T>A​(p.Ser76Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,583,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S76P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000077 (0 hom.)
• Consequence: TP53AIP1 NM_022112.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07421437).

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.226T>A	p.Ser76Thr	missense	Exon 3 of 4	NP_071395.2	Q9HCN2-1
	TP53AIP1	NM_001195194.1		c.226T>A	p.Ser76Thr	missense	Exon 2 of 3	NP_001182123.1	Q9HCN2-4
	TP53AIP1	NM_001195195.2		c.226T>A	p.Ser76Thr	missense	Exon 3 of 4	NP_001182124.1	Q9HCN2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53AIP1	ENST00000531399.6	TSL:1 MANE Select	c.226T>A	p.Ser76Thr	missense	Exon 3 of 4	ENSP00000432743.1	Q9HCN2-1
	TP53AIP1	ENST00000530777.5	TSL:1	c.226T>A	p.Ser76Thr	missense	Exon 2 of 3	ENSP00000432908.1	Q9HCN2-4
	TP53AIP1	ENST00000458238.6	TSL:1	c.226T>A	p.Ser76Thr	missense	Exon 3 of 4	ENSP00000390694.2	Q9HCN2-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000144 AC: 3 AN: 208710 AF XY: 0.0000175

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000312

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000206

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000769 AC: 11 AN: 1431134 Hom.: 0 Cov.: 30 AF XY: 0.00000985 AC XY: 7 AN XY: 710398

African (AFR) AF: 0.0000302 AC: 1 AN: 33158

American (AMR) AF: 0.00 AC: 0 AN: 42746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25800

East Asian (EAS) AF: 0.00 AC: 0 AN: 39094

South Asian (SAS) AF: 0.00 AC: 0 AN: 82898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37088

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000815 AC: 9 AN: 1104790

Other (OTH) AF: 0.0000167 AC: 1 AN: 59808

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152154 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74322

African (AFR) AF: 0.0000241 AC: 1 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.00000874 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.9
DANN	Benign	0.72
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.41
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.95	P
Vest4		0.13
MutPred		0.13		Loss of disorder (P = 0.0745)
MVP		0.11
MPC		0.019
ClinPred		0.081	T
GERP RS		-2.1
Varity_R		0.24
gMVP		0.0027
Mutation Taster		=96/4	polymorphism

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: rs754039433; hg19: chr11-128806460;