12-27958386-C-CA

Variant summary

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

The NM_198965.2(PTHLH):c.*172_*173insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.65 (31626 hom., cov: 0)
  • Exomes 𝑓: 0.47 (16321 hom.)
• Consequence: PTHLH NM_198965.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0210

Genes affected

PTHLH (HGNC:9607): (parathyroid hormone like hormone) The protein encoded by this gene is a member of the parathyroid hormone family. This hormone, via its receptor, PTHR1, regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. It is responsible for most cases of humoral hypercalcemia of malignancy, and mutations in this gene are associated with brachydactyly type E2 (BDE2). Alternatively spliced transcript variants have been found for this gene. There is also evidence for alternative translation initiation from non-AUG (CUG and GUG) start sites, downstream of the initiator AUG codon, resulting in nuclear forms of this hormone. [provided by RefSeq, Nov 2013]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-27958386-C-CA is Benign according to our data. Variant chr12-27958386-C-CA is described in ClinVar as [Benign]. Clinvar id is 1282994.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTHLH	NM_198965.2	c.*172_*173insT		3_prime_UTR_variant	6/6	ENST00000545234.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTHLH	ENST00000545234.6	c.*172_*173insT		3_prime_UTR_variant	6/6	5	NM_198965.2	A1
PTHLH	ENST00000395872.5	c.*172_*173insT		3_prime_UTR_variant	5/5	5		A1
PTHLH	ENST00000539239.5	c.*172_*173insT		3_prime_UTR_variant	3/3	5		A1

Frequencies

GnomAD3 genomes AF: 0.646 AC: 96877 AN: 149958 Hom.: 31599 Cov.: 0

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.615

GnomAD4 exome AF: 0.468 AC: 125656 AN: 268654 Hom.: 16321 Cov.: 6 AF XY: 0.467 AC XY: 63240 AN XY: 135538

Gnomad4 AFR exome AF: 0.562

Gnomad4 AMR exome AF: 0.391

Gnomad4 ASJ exome AF: 0.465

Gnomad4 EAS exome AF: 0.450

Gnomad4 SAS exome AF: 0.386

Gnomad4 FIN exome AF: 0.464

Gnomad4 NFE exome AF: 0.474

Gnomad4 OTH exome AF: 0.463

GnomAD4 genome AF: 0.646 AC: 96943 AN: 150056 Hom.: 31626 Cov.: 0 AF XY: 0.639 AC XY: 46713 AN XY: 73140

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.613

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

Aug 15, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34525777; hg19: chr12-28111319;