rs2522009

Variant names:

• chr11-2403742-G-A
• rs2522009
• NM_005706.4:c.*119G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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]

TRPM5 (HGNC:14323): (transient receptor potential cation channel subfamily M member 5) This gene encodes a member of the transient receptor potential (TRP) protein family, which is a diverse group of proteins with structural features typical of ion channels. This protein plays an important role in taste transduction, and has characteristics of a calcium-activated, non-selective cation channel that carries Na+, K+, and Cs+ ions equally well, but not Ca(2+) ions. It is activated by lower concentrations of intracellular Ca(2+), and inhibited by higher concentrations. It is also a highly temperature-sensitive, heat activated channel showing a steep increase of inward currents at temperatures between 15 and 35 degrees Celsius. This gene is located within the Beckwith-Wiedemann syndrome critical region-1 on chromosome 11p15.5, and has been shown to be imprinted, with exclusive expression from the paternal allele. [provided by RefSeq, Oct 2010]

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 25 AR gene

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.*119G>A		3_prime_UTR	Exon 3 of 3	NP_005697.2
	TSSC4	NM_001297658.2		c.*119G>A		3_prime_UTR	Exon 4 of 4	NP_001284587.1
	TSSC4	NM_001297659.2		c.*119G>A		3_prime_UTR	Exon 3 of 3	NP_001284588.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSSC4	ENST00000333256.11	TSL:1 MANE Select	c.*119G>A		3_prime_UTR	Exon 3 of 3	ENSP00000331087.6
	TSSC4	ENST00000451491.2	TSL:1	c.*119G>A		3_prime_UTR	Exon 2 of 2	ENSP00000411224.2
	TSSC4	ENST00000380996.9	TSL:1	c.*119G>A		3_prime_UTR	Exon 4 of 4	ENSP00000370384.5

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

African (AFR) AF: 0.00210 AC: 42 AN: 20020

American (AMR) AF: 0.00751 AC: 95 AN: 12654

Ashkenazi Jewish (ASJ) AF: 0.00932 AC: 141 AN: 15124

East Asian (EAS) AF: 0.00 AC: 0 AN: 28212

South Asian (SAS) AF: 0.0125 AC: 537 AN: 43066

European-Finnish (FIN) AF: 0.0173 AC: 734 AN: 42474

Middle Eastern (MID) AF: 0.00285 AC: 8 AN: 2810

European-Non Finnish (NFE) AF: 0.0190 AC: 14096 AN: 743572

Other (OTH) AF: 0.0145 AC: 591 AN: 40794

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

African (AFR) AF: 0.00298 AC: 124 AN: 41564

American (AMR) AF: 0.0122 AC: 186 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0132 AC: 64 AN: 4832

European-Finnish (FIN) AF: 0.0137 AC: 146 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0215 AC: 1462 AN: 68004

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.0158 Hom.: 7

Bravo AF: 0.0122

Asia WGS AF: 0.00375 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.2
DANN	Benign	0.85
PhyloP100		0.23
Mutation Taster		=100/0	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: rs2522009; hg19: chr11-2424972;