11-13494832-C-T

Variant names:

• chr11-13494832-C-T
• rs751610
• NM_000315.4:c.-6+1079G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000315.4(PTH):​c.-6+1079G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,102 control chromosomes in the GnomAD database, including 2,609 homozygotes. 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: 𝑓 0.17 (2609 hom., cov: 32)
• Consequence: PTH NM_000315.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.257 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.-6+1079G>A		intron	N/A	NP_000306.1	P01270
	PTH	NM_001316352.2		c.91+1210G>A		intron	N/A	NP_001303281.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTH	ENST00000282091.6	TSL:1 MANE Select	c.-6+1079G>A		intron	N/A	ENSP00000282091.1	P01270
	PTH	ENST00000529816.1	TSL:5	c.-6+1210G>A		intron	N/A	ENSP00000433208.1	P01270

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26413 AN: 151984 Hom.: 2605 Cov.: 32

Gnomad AFR AF: 0.0804

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.174 AC: 26441 AN: 152102 Hom.: 2609 Cov.: 32 AF XY: 0.176 AC XY: 13056 AN XY: 74330

African (AFR) AF: 0.0807 AC: 3352 AN: 41530

American (AMR) AF: 0.263 AC: 4021 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 451 AN: 3466

East Asian (EAS) AF: 0.169 AC: 871 AN: 5164

South Asian (SAS) AF: 0.133 AC: 642 AN: 4824

European-Finnish (FIN) AF: 0.242 AC: 2551 AN: 10560

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13903 AN: 67974

Other (OTH) AF: 0.184 AC: 388 AN: 2112

Alfa AF: 0.110 Hom.: 177

Bravo AF: 0.174

Asia WGS AF: 0.141 AC: 489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.79
DANN	Benign	0.49
PhyloP100		-1.1
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: rs751610; hg19: chr11-13516379;