rs138677805

Variant names:

• chr2-24080835-C-T
• rs138677805
• NM_004881.5:c.603G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-24080835-C-T
• chr2-24080835-C-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_004881.5(TP53I3):​c.603G>A​(p.Thr201Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000516 in 1,614,142 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0026 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (3 hom.)
• Consequence: TP53I3 NM_004881.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.31
• Publications: 0 publications found

Genes affected

TP53I3 (HGNC:19373): (tumor protein p53 inducible protein 3) The protein encoded by this gene is similar to oxidoreductases, which are enzymes involved in cellular responses to oxidative stresses and irradiation. This gene is induced by the tumor suppressor p53 and is thought to be involved in p53-mediated cell death. It contains a p53 consensus binding site in its promoter region and a downstream pentanucleotide microsatellite sequence. P53 has been shown to transcriptionally activate this gene by interacting with the downstream pentanucleotide microsatellite sequence. The microsatellite is polymorphic, with a varying number of pentanucleotide repeats directly correlated with the extent of transcriptional activation by p53. It has been suggested that the microsatellite polymorphism may be associated with differential susceptibility to cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

FAM228B (HGNC:24736): (family with sequence similarity 228 member B)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 2-24080835-C-T is Benign according to our data. Variant chr2-24080835-C-T is described in ClinVar as Benign. ClinVar VariationId is 3050861.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.31 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004881.5. 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
	TP53I3	NM_004881.5	MANE Select	c.603G>A	p.Thr201Thr	synonymous	Exon 3 of 5	NP_004872.2
	TP53I3	NM_147184.4		c.603G>A	p.Thr201Thr	synonymous	Exon 4 of 6	NP_671713.1	Q53FA7-1
	TP53I3	NM_001206802.2		c.603G>A	p.Thr201Thr	synonymous	Exon 3 of 4	NP_001193731.1	Q53FA7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53I3	ENST00000238721.9	TSL:1 MANE Select	c.603G>A	p.Thr201Thr	synonymous	Exon 3 of 5	ENSP00000238721.4	Q53FA7-1
	TP53I3	ENST00000335934.8	TSL:1	c.603G>A	p.Thr201Thr	synonymous	Exon 4 of 6	ENSP00000337834.4	Q53FA7-1
	TP53I3	ENST00000407482.5	TSL:1	c.603G>A	p.Thr201Thr	synonymous	Exon 3 of 4	ENSP00000384414.1	Q53FA7-2

Frequencies

GnomAD3 genomes AF: 0.00257 AC: 391 AN: 152174 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00910

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000676 AC: 170 AN: 251476 AF XY: 0.000456

Gnomad AFR exome AF: 0.00935

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000302 AC: 442 AN: 1461850 Hom.: 3 Cov.: 31 AF XY: 0.000239 AC XY: 174 AN XY: 727210

African (AFR) AF: 0.0102 AC: 341 AN: 33480

American (AMR) AF: 0.000224 AC: 10 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000432 AC: 48 AN: 1112008

Other (OTH) AF: 0.000662 AC: 40 AN: 60394

GnomAD4 genome AF: 0.00257 AC: 391 AN: 152292 Hom.: 3 Cov.: 32 AF XY: 0.00244 AC XY: 182 AN XY: 74470

African (AFR) AF: 0.00907 AC: 377 AN: 41548

American (AMR) AF: 0.000523 AC: 8 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68040

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000886 Hom.: 0

Bravo AF: 0.00349

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TP53I3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.3
DANN	Benign	0.64
PhyloP100		-1.3
Mutation Taster		=99/1	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: rs138677805; hg19: chr2-24303705;