7-142912583-T-C

Position:

• chr7-142912583-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_019841.7(TRPV5):​c.1687A>G​(p.Thr563Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.975 in 1,614,204 control chromosomes in the GnomAD database, including 768,228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.96 (69846 hom., cov: 33)
  • Exomes 𝑓: 0.98 (698382 hom.)
• Consequence: TRPV5 NM_019841.7 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.00

Genes affected

TRPV5 (HGNC:3145): (transient receptor potential cation channel subfamily V member 5) This gene is a member of the transient receptor family and the TrpV subfamily. The calcium-selective channel encoded by this gene has 6 transmembrane-spanning domains, multiple potential phosphorylation sites, an N-linked glycosylation site, and 5 ANK repeats. This protein forms homotetramers or heterotetramers and is activated by a low internal calcium level. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009340793).
• BP6: Variant 7-142912583-T-C is Benign according to our data. Variant chr7-142912583-T-C is described in ClinVar as [Benign]. Clinvar id is 769200.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPV5	NM_019841.7	c.1687A>G	p.Thr563Ala	missense_variant	13/15	ENST00000265310.6	NP_062815.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV5	ENST00000265310.6	c.1687A>G	p.Thr563Ala	missense_variant	13/15	1	NM_019841.7	ENSP00000265310	P1
TRPV5	ENST00000439304.5	c.1522A>G	p.Thr508Ala	missense_variant	12/14	5		ENSP00000406361

Frequencies

GnomAD3 genomes AF: 0.957 AC: 145701 AN: 152194 Hom.: 69807 Cov.: 33

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.970

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.957

GnomAD4 exome AF: 0.977 AC: 1428197 AN: 1461892 Hom.: 698382 Cov.: 84 AF XY: 0.974 AC XY: 708462 AN XY: 727246

Gnomad4 AFR exome AF: 0.907

Gnomad4 AMR exome AF: 0.947

Gnomad4 ASJ exome AF: 0.956

Gnomad4 EAS exome AF: 0.985

Gnomad4 SAS exome AF: 0.882

Gnomad4 FIN exome AF: 0.969

Gnomad4 NFE exome AF: 0.989

Gnomad4 OTH exome AF: 0.969

GnomAD4 genome AF: 0.957 AC: 145796 AN: 152312 Hom.: 69846 Cov.: 33 AF XY: 0.955 AC XY: 71113 AN XY: 74480

Gnomad4 AFR AF: 0.913

Gnomad4 AMR AF: 0.961

Gnomad4 ASJ AF: 0.959

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.963

Gnomad4 NFE AF: 0.986

Gnomad4 OTH AF: 0.959

Alfa AF: 0.980 Hom.: 152192

Bravo AF: 0.958

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

Labcorp Genetics (formerly Invitae), Labcorp

Aug 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_noAF	Pathogenic	0.17
CADD	Benign	12
DEOGEN2	Benign	0.12	T;T
MetaRNN	Benign	0.0093	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.074
gMVP		0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4252499; hg19: chr7-142609749;