chr9-97853077-C-A

Variant names:

• chr9-97853077-C-A
• rs907576
• ENST00000649253.2:n.4G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NR_147055.1(PTCSC2):​n.4G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: PTCSC2 NR_147055.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.485
• Publications: 2 publications found

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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

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>T		non_coding_transcript_exon	Exon 1 of 11
	FOXE1	NM_004473.4	MANE Select	c.-838C>A		upstream_gene	N/A	NP_004464.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTCSC2	ENST00000649253.2		n.4G>T		non_coding_transcript_exon	Exon 1 of 6
	PTCSC2	ENST00000649461.1		n.4G>T		non_coding_transcript_exon	Exon 1 of 11
	PTCSC2	ENST00000649526.1		n.4G>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.3
DANN	Benign	0.89
PhyloP100		-0.48
PromoterAI		-0.016	Neutral

Splicing

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

Other links and lift over

dbSNP: rs907576; hg19: chr9-100615359;