NM_138295.5:c.6180T>C

Variant names:

• chr7-47833247-A-G
• rs921634
• NM_138295.5:c.6180T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_138295.5(PKD1L1):​c.6180T>C​(p.Pro2060Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 1,611,464 control chromosomes in the GnomAD database, including 430,176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (39308 hom., cov: 33)
  • Exomes 𝑓: 0.73 (390868 hom.)
• Consequence: PKD1L1 NM_138295.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.922
• Publications: 17 publications found

Genes affected

PKD1L1 (HGNC:18053): (polycystin 1 like 1, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family containing 11 transmembrane domains, a receptor for egg jelly (REJ) domain, and a polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain. The encoded protein may play a role in the male reproductive system. Alternative splice variants have been described but their biological nature has not been determined. [provided by RefSeq, Jul 2008]

PKD1L1 Gene-Disease associations (from GenCC):

• heterotaxy, visceral, 8, autosomal

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 7-47833247-A-G is Benign according to our data. Variant chr7-47833247-A-G is described in ClinVar as Benign. ClinVar VariationId is 1234377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.922 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138295.5. 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
	PKD1L1	NM_138295.5	MANE Select	c.6180T>C	p.Pro2060Pro	synonymous	Exon 41 of 57	NP_612152.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L1	ENST00000289672.7	TSL:1 MANE Select	c.6180T>C	p.Pro2060Pro	synonymous	Exon 41 of 57	ENSP00000289672.2
	PKD1L1	ENST00000690269.1		c.6180T>C	p.Pro2060Pro	synonymous	Exon 41 of 58	ENSP00000510743.1
	PKD1L1	ENST00000685709.1		c.6012T>C	p.Pro2004Pro	synonymous	Exon 40 of 56	ENSP00000509540.1

Frequencies

GnomAD3 genomes AF: 0.717 AC: 109062 AN: 152038 Hom.: 39277 Cov.: 33

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.709

GnomAD2 exomes AF: 0.732 AC: 181195 AN: 247468 AF XY: 0.726

Gnomad AFR exome AF: 0.668

Gnomad AMR exome AF: 0.764

Gnomad ASJ exome AF: 0.722

Gnomad EAS exome AF: 0.893

Gnomad FIN exome AF: 0.686

Gnomad NFE exome AF: 0.737

Gnomad OTH exome AF: 0.727

GnomAD4 exome AF: 0.731 AC: 1066575 AN: 1459308 Hom.: 390868 Cov.: 52 AF XY: 0.729 AC XY: 529024 AN XY: 725660

African (AFR) AF: 0.663 AC: 22186 AN: 33458

American (AMR) AF: 0.759 AC: 33816 AN: 44536

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 18816 AN: 26086

East Asian (EAS) AF: 0.893 AC: 35430 AN: 39666

South Asian (SAS) AF: 0.649 AC: 55712 AN: 85806

European-Finnish (FIN) AF: 0.687 AC: 36559 AN: 53188

Middle Eastern (MID) AF: 0.692 AC: 3973 AN: 5744

European-Non Finnish (NFE) AF: 0.735 AC: 815805 AN: 1110528

Other (OTH) AF: 0.734 AC: 44278 AN: 60296

GnomAD4 genome AF: 0.717 AC: 109146 AN: 152156 Hom.: 39308 Cov.: 33 AF XY: 0.718 AC XY: 53412 AN XY: 74380

African (AFR) AF: 0.665 AC: 27603 AN: 41500

American (AMR) AF: 0.743 AC: 11364 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2475 AN: 3468

East Asian (EAS) AF: 0.889 AC: 4599 AN: 5174

South Asian (SAS) AF: 0.655 AC: 3157 AN: 4820

European-Finnish (FIN) AF: 0.690 AC: 7298 AN: 10578

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.738 AC: 50215 AN: 68008

Other (OTH) AF: 0.711 AC: 1502 AN: 2112

Alfa AF: 0.730 Hom.: 86385

Bravo AF: 0.721

Asia WGS AF: 0.760 AC: 2640 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Heterotaxy, visceral, 8, autosomal Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.35
DANN	Benign	0.72
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs921634; hg19: chr7-47872845; COSMIC: COSV56962087;