Genetic Variant PTCSC2:n.4G>A (chr9-97853077-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NR_147055.1(PTCSC2):n.4G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,152 control chromosomes in the GnomAD database, including 51,483 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.82 ( 51483 hom., cov: 32)

Consequence

PTCSC2
NR_147055.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.485

Publications

2 publications found

Variant links:

Genes affected

PTCSC2 (HGNC:44086): (papillary thyroid carcinoma susceptibility candidate 2)

PTCSC2 links:

FOXE1 (HGNC:3806): (forkhead box E1) This intronless gene encodes a protein that belongs to the forkhead family of transcription factors. Members of this family contain a conserved 100-amino acid DNA-binding 'forkhead' domain. The encoded protein functions as a thyroid transcription factor that plays a role in thyroid morphogenesis. Mutations in this gene are associated with the Bamforth-Lazarus syndrome, and with susceptibility to nonmedullary thyroid cancer-4. [provided by RefSeq, Nov 2016]

FOXE1 Gene-Disease associations (from GenCC):

Bamforth-Lazarus syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen, Orphanet

FOXE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 9-97853077-C-T is Benign according to our data. Variant chr9-97853077-C-T is described in ClinVar as Benign. ClinVar VariationId is 1250293.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_147055.1. 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
	PTCSC2	NR_147055.1		n.4G>A		non_coding_transcript_exon	Exon 1 of 11
	FOXE1	NM_004473.4	MANE Select	c.-838C>T		upstream_gene	N/A	NP_004464.2

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
PTCSC2	ENST00000649253.2	n.4G>A	non_coding_transcript_exon	Exon 1 of 6
PTCSC2	ENST00000649461.1	n.4G>A	non_coding_transcript_exon	Exon 1 of 11
PTCSC2	ENST00000649526.1	n.4G>A	non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.816

AC:

124137

AN:

152036

Hom.:

51424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.943

Gnomad AMI

AF:

0.582

Gnomad AMR

AF:

0.820

Gnomad ASJ

AF:

0.763

Gnomad EAS

AF:

0.994

Gnomad SAS

AF:

0.801

Gnomad FIN

AF:

0.831

Gnomad MID

AF:

0.812

Gnomad NFE

AF:

0.730

Gnomad OTH

AF:

0.821

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.817

AC:

124248

AN:

152152

Hom.:

51483

Cov.:

AF XY:

0.823

AC XY:

61245

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.943

AC:

39179

AN:

41564

American (AMR)

AF:

0.821

AC:

12558

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.763

AC:

2647

AN:

3468

East Asian (EAS)

AF:

0.994

AC:

5110

AN:

5142

South Asian (SAS)

AF:

0.800

AC:

3858

AN:

4824

European-Finnish (FIN)

AF:

0.831

AC:

8802

AN:

10590

Middle Eastern (MID)

AF:

0.818

AC:

239

AN:

292

European-Non Finnish (NFE)

AF:

0.730

AC:

49590

AN:

67950

Other (OTH)

AF:

0.823

AC:

1738

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1158

2316

3473

4631

5789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

870

1740

2610

3480

4350

<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:

0.767

Hom.:

5307

Bravo

AF:

0.825

Asia WGS

AF:

0.917

AC:

3179

AN:

3466

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.9

(source)

DANN

Benign

0.94

PhyloP100

-0.48

PromoterAI

0.023

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over