11-2402901-T-A

Variant names:

• chr11-2402901-T-A
• NM_005706.4:c.268T>A

Variant summary

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

The NM_005706.4(TSSC4):​c.268T>A​(p.Ser90Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TSSC4 NM_005706.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.97
• Publications: 0 publications found

Genes affected

TSSC4 (HGNC:12386): (tumor suppressing subtransferable candidate 4) This gene is one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. This gene is located among several imprinted genes; however, this gene, as well as the pan-hematopoietic expression gene (PHEMX), escapes imprinting. This gene may play a role in malignancies and disease that involve this region. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

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=0.1979357).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005706.4. 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
	TSSC4	NM_005706.4	MANE Select	c.268T>A	p.Ser90Thr	missense	Exon 3 of 3	NP_005697.2
	TSSC4	NM_001297658.2		c.268T>A	p.Ser90Thr	missense	Exon 4 of 4	NP_001284587.1	Q9Y5U2-1
	TSSC4	NM_001297659.2		c.268T>A	p.Ser90Thr	missense	Exon 3 of 3	NP_001284588.1	Q9Y5U2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSSC4	ENST00000333256.11	TSL:1 MANE Select	c.268T>A	p.Ser90Thr	missense	Exon 3 of 3	ENSP00000331087.6	Q9Y5U2-1
	TSSC4	ENST00000451491.2	TSL:1	c.268T>A	p.Ser90Thr	missense	Exon 2 of 2	ENSP00000411224.2	Q9Y5U2-1
	TSSC4	ENST00000380996.9	TSL:1	c.76T>A	p.Ser26Thr	missense	Exon 4 of 4	ENSP00000370384.5	Q9Y5U2-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 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	0.24
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.031
Eigen_PC	Benign	-0.027
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.0
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.078
Sift	Benign	0.15	T
Sift4G	Benign	0.12	T
Polyphen		0.54	P
Vest4		0.26
MutPred		0.20		Gain of phosphorylation at S90 (P = 0.0584)
MVP		0.36
MPC		0.019
ClinPred		0.49	T
GERP RS		2.2
Varity_R		0.21
gMVP		0.33
Mutation Taster		=84/16	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

hg19: chr11-2424131;