dbSNP rs142462464: TSSC4:p.Glu64Lys (chr11-2402823-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005706.4(TSSC4):c.190G>A(p.Glu64Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000602 in 1,594,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

TSSC4
NM_005706.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.64

Publications

0 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029522687).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSSC4	NM_005706.4	MANE Select	c.190G>A	p.Glu64Lys	missense	Exon 3 of 3	NP_005697.2
TSSC4	NM_001297658.2		c.190G>A	p.Glu64Lys	missense	Exon 4 of 4	NP_001284587.1	Q9Y5U2-1
TSSC4	NM_001297659.2		c.190G>A	p.Glu64Lys	missense	Exon 3 of 3	NP_001284588.1	Q9Y5U2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSSC4	ENST00000333256.11	TSL:1 MANE Select	c.190G>A	p.Glu64Lys	missense	Exon 3 of 3	ENSP00000331087.6	Q9Y5U2-1
TSSC4	ENST00000451491.2	TSL:1	c.190G>A	p.Glu64Lys	missense	Exon 2 of 2	ENSP00000411224.2	Q9Y5U2-1
TSSC4	ENST00000496468.1	TSL:1	c.190G>A	p.Glu64Lys	missense	Exon 2 of 2	ENSP00000435013.1	E9PME3

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000635

AC:

AN:

220360

AF XY:

0.0000418

show subpopulations

Gnomad AFR exome

AF:

0.000908

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:

0.0000207

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000409

AC:

AN:

1442592

Hom.:

Cov.:

AF XY:

0.0000363

AC XY:

AN XY:

716036

show subpopulations

African (AFR)

AF:

0.00112

AC:

AN:

33108

American (AMR)

AF:

0.0000928

AC:

AN:

43118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25694

East Asian (EAS)

AF:

0.00

AC:

AN:

38828

South Asian (SAS)

AF:

0.00

AC:

AN:

83554

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000145

AC:

AN:

1102420

Other (OTH)

AF:

0.0000336

AC:

AN:

59544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000243

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.000821

AC:

AN:

41434

American (AMR)

AF:

0.000196

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000550

Hom.:

Bravo

AF:

0.000310

ESP6500AA

AF:

0.000914

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000746

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.67

M_CAP

Benign

0.020

MetaRNN

Benign

0.030

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

4.6

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.1

REVEL

Benign

0.054

Sift

Benign

0.11

Sift4G

Uncertain

0.034

Polyphen

0.30

Vest4

0.25

MVP

0.17

MPC

0.099

ClinPred

0.042

GERP RS

2.1

BranchPoint Hunter

0.0

Varity_R

0.047

gMVP

0.17

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over