NM_181536.2:c.835-351A>G

Variant names:

• chr16-71984518-T-C
• rs10492825
• NM_181536.2:c.835-351A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181536.2(PKD1L3):​c.835-351A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,238 control chromosomes in the GnomAD database, including 4,105 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (4105 hom., cov: 33)
• Consequence: PKD1L3 NM_181536.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130
• Publications: 9 publications found

Genes affected

PKD1L3 (HGNC:21716): (polycystin 1 like 3, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family. The encoded protein contains 11 transmembrane domains, a latrophilin/CL-1-like GPCR proteolytic site (GPS) domain, and a polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain. This protein may function as a component of cation channel pores.[provided by RefSeq, Apr 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181536.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L3	NM_181536.2	MANE Select	c.835-351A>G		intron	N/A	NP_853514.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L3	ENST00000620267.2	TSL:1 MANE Select	c.835-351A>G		intron	N/A	ENSP00000480090.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31964 AN: 152120 Hom.: 4104 Cov.: 33

Gnomad AFR AF: 0.0788

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.223

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.210 AC: 31965 AN: 152238 Hom.: 4105 Cov.: 33 AF XY: 0.212 AC XY: 15755 AN XY: 74426

African (AFR) AF: 0.0787 AC: 3270 AN: 41560

American (AMR) AF: 0.208 AC: 3190 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 929 AN: 3468

East Asian (EAS) AF: 0.258 AC: 1336 AN: 5170

South Asian (SAS) AF: 0.429 AC: 2070 AN: 4830

European-Finnish (FIN) AF: 0.263 AC: 2781 AN: 10582

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.259 AC: 17627 AN: 68004

Other (OTH) AF: 0.225 AC: 477 AN: 2116

Alfa AF: 0.254 Hom.: 3854

Bravo AF: 0.197

Asia WGS AF: 0.313 AC: 1087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.76
PhyloP100		0.013

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: rs10492825; hg19: chr16-72018417;