NM_181536.2:c.3373G>A

Variant names:

• chr16-71950128-C-T
• rs760164595
• NM_181536.2:c.3373G>A

Variant summary

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

The NM_181536.2(PKD1L3):​c.3373G>A​(p.Glu1125Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000314 in 1,399,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: PKD1L3 NM_181536.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0240
• Publications: 0 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: 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=0.05225444).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L3	NM_181536.2	MANE Select	c.3373G>A	p.Glu1125Lys	missense	Exon 20 of 30	NP_853514.1	Q7Z443

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L3	ENST00000620267.2	TSL:1 MANE Select	c.3373G>A	p.Glu1125Lys	missense	Exon 20 of 30	ENSP00000480090.1	Q7Z443

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000631 AC: 1 AN: 158486 AF XY: 0.00

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.0000314 AC: 44 AN: 1399736 Hom.: 0 Cov.: 33 AF XY: 0.0000290 AC XY: 20 AN XY: 690324

African (AFR) AF: 0.0000317 AC: 1 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25118

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 79190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49564

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5698

European-Non Finnish (NFE) AF: 0.0000343 AC: 37 AN: 1078966

Other (OTH) AF: 0.0000859 AC: 5 AN: 58186

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

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	0.077
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.58
DEOGEN2	Benign	0.020	T
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.052	T
PhyloP100		0.024
PrimateAI	Benign	0.25	T
Sift4G	Benign	0.89	T
Polyphen		0.15	B
Vest4		0.075
MVP		0.12
GERP RS		2.4
Varity_R		0.071
gMVP		0.15

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: rs760164595; hg19: chr16-71984027;