rs111527388

Variant names:

• chr11-13492216-CAA-C
• rs111527388
• NM_000315.4:c.*187_*188delTT

Your query was ambiguous. Multiple possible variants found:

• chr11-13492216-CAA-C
• chr11-13492216-CAA-CA
• chr11-13492216-CAA-CAAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000315.4(PTH):​c.*187_*188delTT 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
• Publications: 0 publications found

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]

PTH Gene-Disease associations (from GenCC):

• hypoparathyroidism, familial isolated 1

  Inheritance: AD, AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• familial isolated hypoparathyroidism due to impaired PTH secretion

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000315.4. 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
	PTH	NM_000315.4	MANE Select	c.*187_*188delTT		3_prime_UTR	Exon 3 of 3	NP_000306.1	P01270
	PTH	NM_001316352.2		c.*187_*188delTT		3_prime_UTR	Exon 3 of 3	NP_001303281.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTH	ENST00000282091.6	TSL:1 MANE Select	c.*187_*188delTT		3_prime_UTR	Exon 3 of 3	ENSP00000282091.1	P01270
	PTH	ENST00000529816.1	TSL:5	c.*187_*188delTT		3_prime_UTR	Exon 3 of 3	ENSP00000433208.1	P01270

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

African (AFR) AF: 0.121 AC: 1518 AN: 12566

American (AMR) AF: 0.0111 AC: 169 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13248

East Asian (EAS) AF: 0.00 AC: 0 AN: 29574

South Asian (SAS) AF: 0.000398 AC: 14 AN: 35176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27204

Middle Eastern (MID) AF: 0.00686 AC: 13 AN: 1896

European-Non Finnish (NFE) AF: 0.000274 AC: 82 AN: 298764

Other (OTH) AF: 0.00964 AC: 248 AN: 25716

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

African (AFR) AF: 0.121 AC: 5029 AN: 41478

American (AMR) AF: 0.0151 AC: 231 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 67970

Other (OTH) AF: 0.0275 AC: 58 AN: 2108

Alfa AF: 0.0272 Hom.: 15

Bravo AF: 0.0398

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs111527388; hg19: chr11-13513763;