NM_003466.4:c.478+16C>G

Variant names:

• chr2-113242674-G-C
• rs773637064
• NM_003466.4:c.478+16C>G

Variant summary

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

The NM_003466.4(PAX8):​c.478+16C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,423,052 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PAX8 NM_003466.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.282
• Publications: 0 publications found

Genes affected

PAX8 (HGNC:8622): (paired box 8) This gene encodes a member of the paired box (PAX) family of transcription factors. Members of this gene family typically encode proteins that contain a paired box domain, an octapeptide, and a paired-type homeodomain. This nuclear protein is involved in thyroid follicular cell development and expression of thyroid-specific genes. Mutations in this gene have been associated with thyroid dysgenesis, thyroid follicular carcinomas and atypical follicular thyroid adenomas. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Mar 2010]

PAX8-AS1 (HGNC:49271): (PAX8 antisense RNA 1)

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=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003466.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX8	NM_003466.4	MANE Select	c.478+16C>G		intron	N/A	NP_003457.1
	PAX8	NM_013952.4		c.478+16C>G		intron	N/A	NP_039246.1
	PAX8	NM_013953.4		c.478+16C>G		intron	N/A	NP_039247.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX8	ENST00000429538.8	TSL:1 MANE Select	c.478+16C>G		intron	N/A	ENSP00000395498.3
	PAX8	ENST00000263334.9	TSL:1	c.478+16C>G		intron	N/A	ENSP00000263334.6
	PAX8	ENST00000348715.9	TSL:1	c.478+16C>G		intron	N/A	ENSP00000314750.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1423052 Hom.: 0 Cov.: 27 AF XY: 0.00000141 AC XY: 1 AN XY: 710506

African (AFR) AF: 0.00 AC: 0 AN: 32750

American (AMR) AF: 0.00 AC: 0 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25912

East Asian (EAS) AF: 0.00 AC: 0 AN: 39496

South Asian (SAS) AF: 0.00 AC: 0 AN: 85418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.29e-7 AC: 1 AN: 1076660

Other (OTH) AF: 0.00 AC: 0 AN: 59080

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.43
DANN	Benign	0.69
PhyloP100		-0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs773637064; hg19: chr2-114000251;