rs201072442

Variant names:

• chr6-52403733-C-T
• rs201072442
• NM_133367.5:c.520C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-52403733-C-T
• chr6-52403733-C-A
• chr6-52403733-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_133367.5(PAQR8):​c.520C>T​(p.Arg174Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000169 in 1,614,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: PAQR8 NM_133367.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.39
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16911691).

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.520C>T	p.Arg174Trp	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.520C>T	p.Arg174Trp	missense	Exon 2 of 2	ENSP00000406197.2	Q8TEZ7
	PAQR8	ENST00000360726.3	TSL:1	c.520C>T	p.Arg174Trp	missense	Exon 3 of 3	ENSP00000353953.3	Q8TEZ7
	PAQR8	ENST00000867242.1		c.520C>T	p.Arg174Trp	missense	Exon 2 of 2	ENSP00000537301.1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000215 AC: 54 AN: 251444 AF XY: 0.000250

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000369

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000172 AC: 251 AN: 1461892 Hom.: 0 Cov.: 34 AF XY: 0.000179 AC XY: 130 AN XY: 727248

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

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

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86256

European-Finnish (FIN) AF: 0.000243 AC: 13 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000183 AC: 204 AN: 1112012

Other (OTH) AF: 0.000281 AC: 17 AN: 60396

GnomAD4 genome AF: 0.000144 AC: 22 AN: 152320 Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74496

African (AFR) AF: 0.0000481 AC: 2 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000277 Hom.: 0

Bravo AF: 0.000140

ExAC AF: 0.000206 AC: 25

EpiCase AF: 0.000545

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

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	0.15
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.4
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.13
Sift	Benign	0.061	T
Sift4G	Benign	0.12	T
Polyphen		0.98	D
Vest4		0.29
MVP		0.68
MPC		0.94
ClinPred		0.10	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.074
gMVP		0.36
Mutation Taster		=80/20	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: rs201072442; hg19: chr6-52268531;