19-56003968-C-T

Variant names:

• chr19-56003968-C-T
• rs1560691
• ENST00000390649.8:c.315C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The ENST00000390649.8(NLRP5):​c.315C>T​(p.Asn105Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,613,728 control chromosomes in the GnomAD database, including 16,254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.16 (2106 hom., cov: 32)
  • Exomes 𝑓: 0.13 (14148 hom.)
• Consequence: NLRP5 ENST00000390649.8 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.73
• Publications: 14 publications found

Genes affected

NLRP5 (HGNC:21269): (NLR family pyrin domain containing 5) The protein encoded by this gene belongs to the NALP protein family. Members of the NALP protein family typically contain a NACHT domain, a NACHT-associated domain (NAD), a C-terminal leucine-rich repeat (LRR) region, and an N-terminal pyrin domain (PYD). Expression of this gene is restricted to the oocyte. A mouse gene that encodes a maternal oocyte protein, similar to this encoded protein, is required for normal early embryogenesis. [provided by RefSeq, Jul 2008]

NLRP5 Gene-Disease associations (from GenCC):

• oocyte/zygote/embryo maturation arrest 19

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 19-56003968-C-T is Benign according to our data. Variant chr19-56003968-C-T is described in ClinVar as Benign. ClinVar VariationId is 3059251.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.73 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000390649.8. 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
	NLRP5	NM_001433705.1		c.162C>T	p.Asn54Asn	synonymous	Exon 2 of 15	NP_001420634.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP5	ENST00000390649.8	TSL:1 MANE Select	c.315C>T	p.Asn105Asn	synonymous	Exon 2 of 15	ENSP00000375063.3	P59047
	NLRP5	ENST00000850973.1		c.162C>T	p.Asn54Asn	synonymous	Exon 2 of 15	ENSP00000521055.1
	NLRP5	ENST00000597673.1	TSL:5	n.234C>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000471494.1	M0R0W4

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23596 AN: 151966 Hom.: 2101 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.134

GnomAD2 exomes AF: 0.166 AC: 41265 AN: 249166 AF XY: 0.157

Gnomad AFR exome AF: 0.189

Gnomad AMR exome AF: 0.284

Gnomad ASJ exome AF: 0.0651

Gnomad EAS exome AF: 0.310

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.113

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.129 AC: 187864 AN: 1461644 Hom.: 14148 Cov.: 33 AF XY: 0.127 AC XY: 92410 AN XY: 727104

African (AFR) AF: 0.193 AC: 6470 AN: 33480

American (AMR) AF: 0.267 AC: 11946 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0661 AC: 1728 AN: 26136

East Asian (EAS) AF: 0.329 AC: 13053 AN: 39700

South Asian (SAS) AF: 0.138 AC: 11906 AN: 86252

European-Finnish (FIN) AF: 0.203 AC: 10826 AN: 53400

Middle Eastern (MID) AF: 0.0928 AC: 535 AN: 5768

European-Non Finnish (NFE) AF: 0.111 AC: 123379 AN: 1111824

Other (OTH) AF: 0.133 AC: 8021 AN: 60374

GnomAD4 genome AF: 0.155 AC: 23621 AN: 152084 Hom.: 2106 Cov.: 32 AF XY: 0.160 AC XY: 11891 AN XY: 74344

African (AFR) AF: 0.192 AC: 7980 AN: 41492

American (AMR) AF: 0.185 AC: 2823 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0749 AC: 260 AN: 3470

East Asian (EAS) AF: 0.314 AC: 1623 AN: 5166

South Asian (SAS) AF: 0.151 AC: 725 AN: 4812

European-Finnish (FIN) AF: 0.212 AC: 2243 AN: 10562

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7525 AN: 67988

Other (OTH) AF: 0.134 AC: 283 AN: 2116

Alfa AF: 0.128 Hom.: 4573

Bravo AF: 0.157

Asia WGS AF: 0.232 AC: 807 AN: 3478

EpiCase AF: 0.105

EpiControl AF: 0.105

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	NLRP5-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.91
DANN	Benign	0.52
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs1560691; hg19: chr19-56515334; COSMIC: COSV66765091;