NM_138295.5:c.399-1381C>T

Variant names:

• chr7-47933437-G-A
• rs6955251
• NM_138295.5:c.399-1381C>T

Variant summary

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

The NM_138295.5(PKD1L1):​c.399-1381C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,944 control chromosomes in the GnomAD database, including 4,151 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 0.23 (4151 hom., cov: 32)
• Consequence: PKD1L1 NM_138295.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 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.399-1381C>T		intron	N/A	NP_612152.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L1	ENST00000289672.7	TSL:1 MANE Select	c.399-1381C>T		intron	N/A	ENSP00000289672.2
	PKD1L1	ENST00000690269.1		c.399-1381C>T		intron	N/A	ENSP00000510743.1
	PKD1L1	ENST00000685709.1		c.399-1381C>T		intron	N/A	ENSP00000509540.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34215 AN: 151824 Hom.: 4136 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.226 AC: 34282 AN: 151944 Hom.: 4151 Cov.: 32 AF XY: 0.227 AC XY: 16842 AN XY: 74278

African (AFR) AF: 0.227 AC: 9409 AN: 41412

American (AMR) AF: 0.249 AC: 3795 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 955 AN: 3470

East Asian (EAS) AF: 0.392 AC: 2015 AN: 5140

South Asian (SAS) AF: 0.367 AC: 1765 AN: 4810

European-Finnish (FIN) AF: 0.171 AC: 1809 AN: 10564

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13941 AN: 67968

Other (OTH) AF: 0.226 AC: 477 AN: 2108

Alfa AF: 0.217 Hom.: 7477

Bravo AF: 0.230

Asia WGS AF: 0.352 AC: 1222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.8
DANN	Benign	0.53
PhyloP100		-0.54
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: rs6955251; hg19: chr7-47973034;