chr11-2402868-C-T

Variant names:

• chr11-2402868-C-T
• rs375009638
• NM_005706.4:c.235C>T

Variant summary

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

The NM_005706.4(TSSC4):​c.235C>T​(p.Pro79Ser) 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. 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. P79T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TSSC4 NM_005706.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3092765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSSC4	NM_005706.4	c.235C>T	p.Pro79Ser	missense_variant	Exon 3 of 3	ENST00000333256.11	NP_005697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSSC4	ENST00000333256.11	c.235C>T	p.Pro79Ser	missense_variant	Exon 3 of 3	1	NM_005706.4	ENSP00000331087.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 246256 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	.;T;T;T;T;T;.;.;T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.85	T;.;D;D;D;D;D;D;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.31	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.2	.;M;.;.;.;.;.;.;M
PhyloP100		1.2
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.3	D;D;D;N;D;D;D;N;D
REVEL	Benign	0.12
Sift	Benign	0.047	D;D;T;T;D;D;T;T;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D
Polyphen		1.0	D;D;.;.;.;.;.;.;D
Vest4		0.44
MutPred		0.38		.;Gain of MoRF binding (P = 0.0519);.;Gain of MoRF binding (P = 0.0519);Gain of MoRF binding (P = 0.0519);Gain of MoRF binding (P = 0.0519);.;Gain of MoRF binding (P = 0.0519);Gain of MoRF binding (P = 0.0519);
MVP		0.35
MPC		0.13
ClinPred		0.94	D
GERP RS		3.4
Varity_R		0.077
gMVP		0.29
Mutation Taster		=77/23	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: rs375009638; hg19: chr11-2424098;