rs953718297

Variant names:

• chr22-46257040-C-A
• rs953718297
• NM_006071.2:c.6283G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-46257040-C-A
• chr22-46257040-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006071.2(PKDREJ):​c.6283G>T​(p.Val2095Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,642 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V2095I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PKDREJ NM_006071.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 0 publications found

Genes affected

PKDREJ (HGNC:9015): (polycystin family receptor for egg jelly) This intronless gene encodes a member of the polycystin protein family. The encoded protein contains 11 transmembrane domains, a receptor for egg jelly (REJ) domain, a G-protein-coupled receptor proteolytic site (GPS) domain, and a polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain. This protein may play a role in human reproduction. Alternative splice variants have been described but their biological natures have not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006071.2. 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
	PKDREJ	NM_006071.2	MANE Select	c.6283G>T	p.Val2095Phe	missense	Exon 1 of 1	NP_006062.1	Q9NTG1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKDREJ	ENST00000253255.7	TSL:6 MANE Select	c.6283G>T	p.Val2095Phe	missense	Exon 1 of 1	ENSP00000253255.5	Q9NTG1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250786 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461642 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727086

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111974

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.12
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.48
Sift	Benign	0.15	T
Sift4G	Uncertain	0.016	D
Polyphen		0.98	D
Vest4		0.40
MutPred		0.70		Loss of catalytic residue at V2095 (P = 0.1562)
MVP		0.50
ClinPred		0.68	D
GERP RS		0.99
Varity_R		0.083
gMVP		0.72
Mutation Taster		=71/29	polymorphism

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: rs953718297; hg19: chr22-46652937;