9-97853077-C-T

Variant names:

• chr9-97853077-C-T
• rs907576
• ENST00000649461.1:n.4G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.485

Genes affected

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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCSC2	NR_147055.1	n.4G>A		non_coding_transcript_exon_variant	Exon 1 of 11
FOXE1	NM_004473.4	c.-838C>T		upstream_gene_variant		ENST00000375123.5	NP_004464.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCSC2	ENST00000649461.1	n.4G>A		non_coding_transcript_exon_variant	Exon 1 of 11
PTCSC2	ENST00000649526.1	n.4G>A		non_coding_transcript_exon_variant	Exon 1 of 3
PTCSC2	ENST00000650104.1	n.4G>A		non_coding_transcript_exon_variant	Exon 1 of 3
FOXE1	ENST00000375123.5	c.-838C>T		upstream_gene_variant		6	NM_004473.4	ENSP00000364265.3

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124137 AN: 152036 Hom.: 51424 Cov.: 32

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.: 32 AF XY: 0.823 AC XY: 61245 AN XY: 74374

Gnomad4 AFR AF: 0.943

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.831

Gnomad4 NFE AF: 0.730

Gnomad4 OTH AF: 0.823

Alfa AF: 0.767 Hom.: 5307

Bravo AF: 0.825

Asia WGS AF: 0.917 AC: 3179 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.9
DANN	Benign	0.94

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs907576; hg19: chr9-100615359;