rs148777835

Variant names:

• chr1-3683128-C-A
• rs148777835
• NM_005427.4:c.134C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-3683128-C-A
• chr1-3683128-C-G
• chr1-3683128-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005427.4(TP73):​c.134C>A​(p.Thr45Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. T45M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TP73 NM_005427.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00
• Publications: 0 publications found

Genes affected

TP73 (HGNC:12003): (tumor protein p73) This gene encodes a member of the p53 family of transcription factors involved in cellular responses to stress and development. It maps to a region on chromosome 1p36 that is frequently deleted in neuroblastoma and other tumors, and thought to contain multiple tumor suppressor genes. The demonstration that this gene is monoallelically expressed (likely from the maternal allele), supports the notion that it is a candidate gene for neuroblastoma. Many transcript variants resulting from alternative splicing and/or use of alternate promoters have been found for this gene, but the biological validity and the full-length nature of some variants have not been determined. [provided by RefSeq, Feb 2011]

TP73 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 47, and lissencephaly

  Inheritance: AR Classification: STRONG Submitted by: ClinGen, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2948733).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005427.4. 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
	TP73	NM_005427.4	MANE Select	c.134C>A	p.Thr45Lys	missense	Exon 3 of 14	NP_005418.1	O15350-1
	TP73	NM_001204187.2		c.134C>A	p.Thr45Lys	missense	Exon 3 of 12	NP_001191116.1	O15350-13
	TP73	NM_001204188.2		c.134C>A	p.Thr45Lys	missense	Exon 3 of 12	NP_001191117.1	O15350-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP73	ENST00000378295.9	TSL:1 MANE Select	c.134C>A	p.Thr45Lys	missense	Exon 3 of 14	ENSP00000367545.4	O15350-1
	TP73	ENST00000713570.1		c.134C>A	p.Thr45Lys	missense	Exon 3 of 14	ENSP00000518863.1	O15350-1
	TP73	ENST00000713572.1		c.134C>A	p.Thr45Lys	missense	Exon 3 of 14	ENSP00000518864.1	O15350-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Uncertain	0.51	D
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.70	D
MetaRNN	Benign	0.29	T
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	0.81	L
PhyloP100		4.0
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.34
Sift	Benign	0.060	T
Sift4G	Benign	0.37	T
Polyphen		0.22	B
Vest4		0.34
MutPred		0.35		Gain of ubiquitination at T45 (P = 0.0045)
MVP		0.57
MPC		0.20
ClinPred		0.30	T
GERP RS		3.8
Varity_R		0.080
gMVP		0.59
Mutation Taster		=88/12	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: rs148777835; hg19: chr1-3599692;