chr15-69397560-A-G

Variant names:

• chr15-69397560-A-G
• rs371703378
• NM_017705.4:c.605A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_017705.4(PAQR5):​c.605A>G​(p.Tyr202Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000118 in 1,597,872 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 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: PAQR5 NM_017705.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17
• Publications: 1 publications found

Genes affected

PAQR5 (HGNC:29645): (progestin and adipoQ receptor family member 5) Predicted to enable signaling receptor activity. Predicted to be involved in oogenesis. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

KIF23-AS1 (HGNC:27075): (KIF23 and PAQR5 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3908596).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017705.4. 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
	PAQR5	NM_017705.4	MANE Select	c.605A>G	p.Tyr202Cys	missense	Exon 7 of 9	NP_060175.3
	PAQR5	NM_001104554.2		c.605A>G	p.Tyr202Cys	missense	Exon 7 of 9	NP_001098024.1	Q9NXK6
	KIF23-AS1	NR_132970.1		n.1122T>C		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAQR5	ENST00000395407.7	TSL:1 MANE Select	c.605A>G	p.Tyr202Cys	missense	Exon 7 of 9	ENSP00000378803.2	Q9NXK6
	PAQR5	ENST00000340965.4	TSL:1	c.605A>G	p.Tyr202Cys	missense	Exon 5 of 7	ENSP00000343877.3	Q9NXK6
	PAQR5	ENST00000561153.5	TSL:5	c.605A>G	p.Tyr202Cys	missense	Exon 7 of 9	ENSP00000453526.1	Q9NXK6

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 151976 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000477 AC: 12 AN: 251484 AF XY: 0.0000589

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000967

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000118 AC: 171 AN: 1445896 Hom.: 0 Cov.: 26 AF XY: 0.000130 AC XY: 94 AN XY: 720450

African (AFR) AF: 0.0000603 AC: 2 AN: 33142

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26018

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.00 AC: 0 AN: 85942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.000144 AC: 158 AN: 1097438

Other (OTH) AF: 0.000184 AC: 11 AN: 59896

GnomAD4 genome AF: 0.000112 AC: 17 AN: 151976 Hom.: 0 Cov.: 32 AF XY: 0.0000809 AC XY: 6 AN XY: 74206

African (AFR) AF: 0.0000483 AC: 2 AN: 41372

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 67996

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.000115 Hom.: 0

Bravo AF: 0.000117

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.00

EpiControl AF: 0.000178

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	0.065
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.031
Eigen_PC	Benign	0.0038
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.0	T
PhyloP100		4.2
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.018	D
Polyphen		0.14	B
Vest4		0.53
MVP		0.40
MPC		0.26
ClinPred		0.39	T
GERP RS		1.3
Varity_R		0.70
gMVP		0.72
Mutation Taster		=28/72	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs371703378; hg19: chr15-69689899; COSMIC: COSV104653379;