7-142912583-T-C

Variant names:

• chr7-142912583-T-C
• rs4252499
• NM_019841.7:c.1687A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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]

TRPV5 Gene-Disease associations (from GenCC):

• hypercalciuria, absorptive, 2

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019841.7. 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
	TRPV5	NM_019841.7	MANE Select	c.1687A>G	p.Thr563Ala	missense	Exon 13 of 15	NP_062815.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPV5	ENST00000265310.6	TSL:1 MANE Select	c.1687A>G	p.Thr563Ala	missense	Exon 13 of 15	ENSP00000265310.1	Q9NQA5-1
	TRPV5	ENST00000439304.5	TSL:5	c.1522A>G	p.Thr508Ala	missense	Exon 12 of 14	ENSP00000406361.1	H7C2J6

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

African (AFR) AF: 0.907 AC: 30366 AN: 33480

American (AMR) AF: 0.947 AC: 42354 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.956 AC: 24980 AN: 26136

East Asian (EAS) AF: 0.985 AC: 39100 AN: 39700

South Asian (SAS) AF: 0.882 AC: 76089 AN: 86258

European-Finnish (FIN) AF: 0.969 AC: 51755 AN: 53420

Middle Eastern (MID) AF: 0.959 AC: 5533 AN: 5768

European-Non Finnish (NFE) AF: 0.989 AC: 1099513 AN: 1112010

Other (OTH) AF: 0.969 AC: 58507 AN: 60396

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

African (AFR) AF: 0.913 AC: 37950 AN: 41550

American (AMR) AF: 0.961 AC: 14708 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3331 AN: 3472

East Asian (EAS) AF: 0.987 AC: 5117 AN: 5182

South Asian (SAS) AF: 0.865 AC: 4175 AN: 4824

European-Finnish (FIN) AF: 0.963 AC: 10228 AN: 10618

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.986 AC: 67101 AN: 68048

Other (OTH) AF: 0.959 AC: 2025 AN: 2112

Alfa AF: 0.979 Hom.: 290119

Bravo AF: 0.958

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
AlphaMissense	Benign	0.070
BayesDel_noAF	Pathogenic	0.17
CADD	Benign	12
DEOGEN2	Benign	0.12	T
MetaRNN	Benign	0.0093	T
PhyloP100		1.0
Sift4G	Benign	1.0	T
Vest4		0.074
gMVP		0.62

Splicing

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

Other links and lift over

dbSNP: rs4252499; hg19: chr7-142609749;