rs144826376

Variant names:

• chr6-52403532-A-C
• rs144826376
• NM_133367.5:c.319A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-52403532-A-C
• chr6-52403532-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_133367.5(PAQR8):​c.319A>C​(p.Thr107Pro) 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. 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. T107A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PAQR8 NM_133367.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042480707).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAQR8	NM_133367.5	c.319A>C	p.Thr107Pro	missense_variant	Exon 2 of 2	ENST00000442253.3	NP_588608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAQR8	ENST00000442253.3	c.319A>C	p.Thr107Pro	missense_variant	Exon 2 of 2	1	NM_133367.5	ENSP00000406197.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.13
DANN	Benign	0.062
DEOGEN2	Benign	0.042	.;T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.37	T;.;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.042	T;T;T
MetaSVM	Benign	-0.94	T
PhyloP100		-0.092
PrimateAI	Benign	0.35	T
PROVEAN	Benign	2.2	N;N;N
REVEL	Benign	0.033
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.41	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.042
MutPred		0.61		Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP		0.20
MPC		0.49
ClinPred		0.028	T
GERP RS		-3.3
Varity_R		0.040
gMVP		0.29
Mutation Taster		=91/9	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: rs144826376; hg19: chr6-52268330;