rs4987682

Variant names:

• chr7-142871843-A-C
• NM_018646.6:c.2162T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-142871843-A-C
• chr7-142871843-A-G
• chr7-142871843-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018646.6(TRPV6):​c.2162T>G​(p.Met721Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M721T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRPV6 NM_018646.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

Genes affected

TRPV6 (HGNC:14006): (transient receptor potential cation channel subfamily V member 6) This gene encodes a member of a family of multipass membrane proteins that functions as calcium channels. The encoded protein contains N-terminal ankyrin repeats, which are required for channel assembly and regulation. Translation initiation for this protein occurs at a non-AUG start codon that is decoded as methionine. This gene is situated next to a closely related gene for transient receptor potential cation channel subfamily V member 5 (TRPV5). This locus has experienced positive selection in non-African populations, resulting in several non-synonymous codon differences among individuals of different genetic backgrounds. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07815081).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV6	NM_018646.6	c.2162T>G	p.Met721Arg	missense_variant	Exon 15 of 15	ENST00000359396.9	NP_061116.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV6	ENST00000359396.9	c.2162T>G	p.Met721Arg	missense_variant	Exon 15 of 15	1	NM_018646.6	ENSP00000352358.5
TRPV6	ENST00000485138.5	n.1772T>G		non_coding_transcript_exon_variant	Exon 9 of 9	2
TRPV6	ENST00000615386.4	n.9803T>G		non_coding_transcript_exon_variant	Exon 12 of 12	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.5
DANN	Benign	0.70
DEOGEN2	Benign	0.18	.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.16	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.078	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.33	T
REVEL	Benign	0.046
Sift4G	Benign	0.54	T;.
Vest4		0.098
MVP		0.085
MPC		0.43
ClinPred		0.15	T
GERP RS		1.3
Varity_R		0.24
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-142569596;