rs1763880071

Variant names:

• chr6-52404172-T-C
• rs1763880071
• NM_133367.5:c.959T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133367.5(PAQR8):​c.959T>C​(p.Val320Ala) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PAQR8 NM_133367.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.96
• Publications: 0 publications found

Genes affected

PAQR8 (HGNC:15708): (progestin and adipoQ receptor family member 8) Predicted to enable steroid binding activity and steroid hormone receptor activity. Predicted to be involved in response to steroid hormone. Located in Golgi apparatus and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

EFHC1 (HGNC:16406): (EF-hand domain containing 1) This gene encodes an EF-hand-containing calcium binding protein. The encoded protein likely plays a role in calcium homeostasis. Mutations in this gene have been associated with susceptibility to juvenile myoclonic epilepsy and juvenile absence epilepsy. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

EFHC1 Gene-Disease associations (from GenCC):

• juvenile myoclonic epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• epilepsy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000295329 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.107283115).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133367.5. 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
	PAQR8	NM_133367.5	MANE Select	c.959T>C	p.Val320Ala	missense	Exon 2 of 2	NP_588608.1	Q8TEZ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAQR8	ENST00000442253.3	TSL:1 MANE Select	c.959T>C	p.Val320Ala	missense	Exon 2 of 2	ENSP00000406197.2	Q8TEZ7
	PAQR8	ENST00000360726.3	TSL:1	c.959T>C	p.Val320Ala	missense	Exon 3 of 3	ENSP00000353953.3	Q8TEZ7
	PAQR8	ENST00000867242.1		c.959T>C	p.Val320Ala	missense	Exon 2 of 2	ENSP00000537301.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Benign	0.91
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.026
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.0
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.024
Sift	Benign	0.57	T
Sift4G	Benign	0.58	T
Polyphen		0.020	B
Vest4		0.26
MutPred		0.38		Loss of stability (P = 0.1691)
MVP		0.35
MPC		0.47
ClinPred		0.21	T
GERP RS		5.5
Varity_R		0.038
gMVP		0.54
Mutation Taster		=84/16	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: rs1763880071; hg19: chr6-52268970;