chr11-128936567-C-G

Variant names:

• chr11-128936567-C-G
• rs370056266
• NM_022112.3:c.224G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_022112.3(TP53AIP1):​c.224G>C​(p.Trp75Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000602 in 1,583,734 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00063 (0 hom.)
• Consequence: TP53AIP1 NM_022112.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.81
• Publications: 2 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02462852).

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.224G>C	p.Trp75Ser	missense	Exon 3 of 4	NP_071395.2	Q9HCN2-1
	TP53AIP1	NM_001195194.1		c.224G>C	p.Trp75Ser	missense	Exon 2 of 3	NP_001182123.1	Q9HCN2-4
	TP53AIP1	NM_001195195.2		c.224G>C	p.Trp75Ser	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.224G>C	p.Trp75Ser	missense	Exon 3 of 4	ENSP00000432743.1	Q9HCN2-1
	TP53AIP1	ENST00000530777.5	TSL:1	c.224G>C	p.Trp75Ser	missense	Exon 2 of 3	ENSP00000432908.1	Q9HCN2-4
	TP53AIP1	ENST00000458238.6	TSL:1	c.224G>C	p.Trp75Ser	missense	Exon 3 of 4	ENSP00000390694.2	Q9HCN2-2

Frequencies

GnomAD3 genomes AF: 0.000335 AC: 51 AN: 152076 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000647

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000338 AC: 71 AN: 209828 AF XY: 0.000287

Gnomad AFR exome AF: 0.000166

Gnomad AMR exome AF: 0.0000311

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000686

Gnomad OTH exome AF: 0.000183

GnomAD4 exome AF: 0.000631 AC: 903 AN: 1431658 Hom.: 0 Cov.: 30 AF XY: 0.000580 AC XY: 412 AN XY: 710736

African (AFR) AF: 0.000151 AC: 5 AN: 33182

American (AMR) AF: 0.0000233 AC: 1 AN: 42846

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25814

East Asian (EAS) AF: 0.00 AC: 0 AN: 39068

South Asian (SAS) AF: 0.00 AC: 0 AN: 82954

European-Finnish (FIN) AF: 0.0000269 AC: 1 AN: 37128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.000776 AC: 858 AN: 1105090

Other (OTH) AF: 0.000635 AC: 38 AN: 59820

GnomAD4 genome AF: 0.000335 AC: 51 AN: 152076 Hom.: 1 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74276

African (AFR) AF: 0.000121 AC: 5 AN: 41414

American (AMR) AF: 0.000131 AC: 2 AN: 15250

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000647 AC: 44 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000427 Hom.: 0

Bravo AF: 0.000416

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000755 AC: 3

ExAC AF: 0.000288 AC: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	7.9
DANN	Benign	0.74
DEOGEN2	Benign	0.053	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.8
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.062
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.018	B
Vest4		0.34
MVP		0.10
MPC		0.036
ClinPred		0.052	T
GERP RS		-3.8
Varity_R		0.26
gMVP		0.010
Mutation Taster		=100/0	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: rs370056266; hg19: chr11-128806462;