chr11-13492216-CAA-C

Position:

• chr11-13492216-CAA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000315.4(PTH):​c.*187_*188del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 611,540 control chromosomes in the GnomAD database, including 419 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (302 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (117 hom.)
• Consequence: PTH NM_000315.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.19

Genes affected

PTH (HGNC:9606): (parathyroid hormone) This gene encodes a member of the parathyroid family of proteins. The encoded preproprotein is proteolytically processed to generate a protein that binds to the parathyroid hormone/parathyroid hormone-related peptide receptor and regulates blood calcium and phosphate levels. Excess production of the encoded protein, known as hyperparathyroidism, can result in hypercalcemia and kidney stones. On the other hand, defective processing of the encoded protein may lead to hypoparathyroidism, which can result in hypocalcemia and numbness. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-13492216-CAA-C is Benign according to our data. Variant chr11-13492216-CAA-C is described in ClinVar as [Benign]. Clinvar id is 1178813.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTH	NM_000315.4	c.*187_*188del		3_prime_UTR_variant	3/3	ENST00000282091.6
PTH	NM_001316352.2	c.*187_*188del		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTH	ENST00000282091.6	c.*187_*188del		3_prime_UTR_variant	3/3	1	NM_000315.4	P1
PTH	ENST00000529816.1	c.*187_*188del		3_prime_UTR_variant	3/3	5		P1

Frequencies

GnomAD3 genomes AF: 0.0351 AC: 5332 AN: 152004 Hom.: 300 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0278

GnomAD4 exome AF: 0.00445 AC: 2044 AN: 459416 Hom.: 117 AF XY: 0.00363 AC XY: 866 AN XY: 238746

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.0111

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000398

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000274

Gnomad4 OTH exome AF: 0.00964

GnomAD4 genome AF: 0.0352 AC: 5357 AN: 152124 Hom.: 302 Cov.: 32 AF XY: 0.0339 AC XY: 2519 AN XY: 74380

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.0151

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.0272 Hom.: 15

Bravo AF: 0.0398

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs111527388; hg19: chr11-13513763;