rs2522009

Positions:

• chr11-2403742-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005706.4(TSSC4):​c.*119G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 1,101,014 control chromosomes in the GnomAD database, including 186 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.014 (25 hom., cov: 33)
  • Exomes 𝑓: 0.017 (161 hom.)
• Consequence: TSSC4 NM_005706.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226

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]

TSSC4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0136 (2071/152288) while in subpopulation NFE AF= 0.0215 (1462/68004). AF 95% confidence interval is 0.0206. There are 25 homozygotes in gnomad4. There are 984 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSSC4	NM_005706.4	c.*119G>A		3_prime_UTR_variant	3/3	ENST00000333256.11	NP_005697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSSC4	ENST00000333256.11	c.*119G>A		3_prime_UTR_variant	3/3	1	NM_005706.4	ENSP00000331087.6

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2067 AN: 152170 Hom.: 24 Cov.: 33

Gnomad AFR AF: 0.00299

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0215

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.0171 AC: 16244 AN: 948726 Hom.: 161 Cov.: 13 AF XY: 0.0170 AC XY: 7921 AN XY: 464580

Gnomad4 AFR exome AF: 0.00210

Gnomad4 AMR exome AF: 0.00751

Gnomad4 ASJ exome AF: 0.00932

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0125

Gnomad4 FIN exome AF: 0.0173

Gnomad4 NFE exome AF: 0.0190

Gnomad4 OTH exome AF: 0.0145

GnomAD4 genome AF: 0.0136 AC: 2071 AN: 152288 Hom.: 25 Cov.: 33 AF XY: 0.0132 AC XY: 984 AN XY: 74458

Gnomad4 AFR AF: 0.00298

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0132

Gnomad4 FIN AF: 0.0137

Gnomad4 NFE AF: 0.0215

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0167 Hom.: 7

Bravo AF: 0.0122

Asia WGS AF: 0.00375 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.2
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs2522009; hg19: chr11-2424972;