rs199743434

Variant names:

• chr20-34709316-G-C
• rs199743434
• NM_021202.3:c.205G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-34709316-G-C
• chr20-34709316-G-A
• chr20-34709316-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_021202.3(TP53INP2):​c.205G>C​(p.Glu69Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000316 in 1,613,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (0 hom.)
• Consequence: TP53INP2 NM_021202.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.85
• Publications: 2 publications found

Genes affected

TP53INP2 (HGNC:16104): (tumor protein p53 inducible nuclear protein 2) The protein encoded by this gene promotes autophagy and is essential for proper autophagosome formation and processing. In addition, the encoded protein can enhance rDNA transcription by helping in the assembly of the POLR1/RNA polymerase I preinitiation complex. Finally, this protein serves as a transcriptional activator for some genes. [provided by RefSeq, Jul 2016]

NCOA6 (HGNC:15936): (nuclear receptor coactivator 6) The protein encoded by this gene is a transcriptional coactivator that can interact with nuclear hormone receptors to enhance their transcriptional activator functions. This protein has been shown to be involved in the hormone-dependent coactivation of several receptors, including prostanoid, retinoid, vitamin D3, thyroid hormone, and steroid receptors. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jun 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3061951).
• BS2: High AC in GnomAd4 at 62 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021202.3. 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
	TP53INP2	NM_021202.3	MANE Select	c.205G>C	p.Glu69Gln	missense	Exon 4 of 5	NP_067025.1	Q8IXH6
	TP53INP2	NM_001329429.2		c.205G>C	p.Glu69Gln	missense	Exon 4 of 5	NP_001316358.1	Q8IXH6
	TP53INP2	NM_001329430.2		c.205G>C	p.Glu69Gln	missense	Exon 3 of 4	NP_001316359.1	Q8IXH6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53INP2	ENST00000374810.8	TSL:1 MANE Select	c.205G>C	p.Glu69Gln	missense	Exon 4 of 5	ENSP00000363943.3	Q8IXH6
	TP53INP2	ENST00000374809.6	TSL:5	c.205G>C	p.Glu69Gln	missense	Exon 3 of 4	ENSP00000363942.2	Q8IXH6
	TP53INP2	ENST00000894582.1		c.205G>C	p.Glu69Gln	missense	Exon 3 of 4	ENSP00000564641.1

Frequencies

GnomAD3 genomes AF: 0.000408 AC: 62 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000721

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000317 AC: 77 AN: 243070 AF XY: 0.000346

Gnomad AFR exome AF: 0.000202

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00121

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000515

Gnomad NFE exome AF: 0.000453

Gnomad OTH exome AF: 0.000335

GnomAD4 exome AF: 0.000307 AC: 448 AN: 1460888 Hom.: 0 Cov.: 36 AF XY: 0.000337 AC XY: 245 AN XY: 726778

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.0000224 AC: 1 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.000958 AC: 25 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86236

European-Finnish (FIN) AF: 0.000756 AC: 40 AN: 52906

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000330 AC: 367 AN: 1111712

Other (OTH) AF: 0.000199 AC: 12 AN: 60322

GnomAD4 genome AF: 0.000407 AC: 62 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.000416 AC XY: 31 AN XY: 74442

African (AFR) AF: 0.0000481 AC: 2 AN: 41546

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000721 AC: 49 AN: 67980

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000525 Hom.: 0

Bravo AF: 0.000261

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.000338 AC: 41

EpiCase AF: 0.000600

EpiControl AF: 0.000178

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	Pathogenic	0.84
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	0.13	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		9.8
PrimateAI	Pathogenic	0.94	D
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.45
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.85
MVP		0.59
MPC		0.86
ClinPred		0.49	T
GERP RS		4.6
Varity_R		0.77
gMVP		0.56
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs199743434; hg19: chr20-33297120;