chr16-71934024-C-T

Variant names:

• chr16-71934024-C-T
• rs17358402
• NM_181536.2:c.4715G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181536.2(PKD1L3):​c.4715G>A​(p.Arg1572His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,551,614 control chromosomes in the GnomAD database, including 48,053 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3597 hom., cov: 32)
  • Exomes 𝑓: 0.25 (44456 hom.)
• Consequence: PKD1L3 NM_181536.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.106
• Publications: 13 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003930241).
• BP6: Variant 16-71934024-C-T is Benign according to our data. Variant chr16-71934024-C-T is described in ClinVar as Benign. ClinVar VariationId is 1221070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L3	NM_181536.2	MANE Select	c.4715G>A	p.Arg1572His	missense	Exon 27 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.4715G>A	p.Arg1572His	missense	Exon 27 of 30	ENSP00000480090.1	Q7Z443

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30136 AN: 152000 Hom.: 3593 Cov.: 32

Gnomad AFR AF: 0.0834

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.0547

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.223

GnomAD2 exomes AF: 0.206 AC: 32454 AN: 157162 AF XY: 0.208

Gnomad AFR exome AF: 0.0835

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.317

Gnomad EAS exome AF: 0.0511

Gnomad FIN exome AF: 0.235

Gnomad NFE exome AF: 0.271

Gnomad OTH exome AF: 0.235

GnomAD4 exome AF: 0.246 AC: 343692 AN: 1399496 Hom.: 44456 Cov.: 36 AF XY: 0.244 AC XY: 168397 AN XY: 690240

African (AFR) AF: 0.0821 AC: 2595 AN: 31598

American (AMR) AF: 0.144 AC: 5154 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 7990 AN: 25180

East Asian (EAS) AF: 0.0474 AC: 1693 AN: 35740

South Asian (SAS) AF: 0.156 AC: 12378 AN: 79236

European-Finnish (FIN) AF: 0.235 AC: 11593 AN: 49288

Middle Eastern (MID) AF: 0.293 AC: 1668 AN: 5702

European-Non Finnish (NFE) AF: 0.266 AC: 287032 AN: 1079000

Other (OTH) AF: 0.234 AC: 13589 AN: 58048

GnomAD4 genome AF: 0.198 AC: 30159 AN: 152118 Hom.: 3597 Cov.: 32 AF XY: 0.197 AC XY: 14678 AN XY: 74344

African (AFR) AF: 0.0839 AC: 3484 AN: 41514

American (AMR) AF: 0.177 AC: 2708 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1142 AN: 3466

East Asian (EAS) AF: 0.0547 AC: 283 AN: 5176

South Asian (SAS) AF: 0.161 AC: 779 AN: 4824

European-Finnish (FIN) AF: 0.253 AC: 2675 AN: 10572

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18338 AN: 67982

Other (OTH) AF: 0.220 AC: 464 AN: 2110

Alfa AF: 0.243 Hom.: 17498

Bravo AF: 0.188

TwinsUK AF: 0.267 AC: 989

ALSPAC AF: 0.272 AC: 1050

ESP6500AA AF: 0.103 AC: 142

ESP6500EA AF: 0.275 AC: 874

ExAC AF: 0.191 AC: 4868

Asia WGS AF: 0.0950 AC: 332 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	0.039
DANN	Benign	0.67
DEOGEN2	Benign	0.13	T
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0039	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.11
PrimateAI	Benign	0.26	T
Sift4G	Benign	0.34	T
Polyphen		0.021	B
Vest4		0.046
GERP RS		-9.4
Varity_R		0.026
gMVP		0.47

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: rs17358402; hg19: chr16-71967927; COSMIC: COSV58663694; COSMIC: COSV58663694;