rs921634

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-47833247-A-C
• chr7-47833247-A-G
• chr7-47833247-A-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_138295.5(PKD1L1):​c.6180T>G​(p.Pro2060Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P2060P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PKD1L1 NM_138295.5 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-0.922 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L1	NM_138295.5	c.6180T>G	p.Pro2060Pro	synonymous_variant	Exon 41 of 57	ENST00000289672.7	NP_612152.1
PKD1L1	XM_017011798.3	c.6357T>G	p.Pro2119Pro	synonymous_variant	Exon 42 of 59		XP_016867287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L1	ENST00000289672.7	c.6180T>G	p.Pro2060Pro	synonymous_variant	Exon 41 of 57	1	NM_138295.5	ENSP00000289672.2
PKD1L1	ENST00000690269.1	c.6180T>G	p.Pro2060Pro	synonymous_variant	Exon 41 of 58			ENSP00000510743.1
PKD1L1	ENST00000685709.1	c.6012T>G	p.Pro2004Pro	synonymous_variant	Exon 40 of 56			ENSP00000509540.1
PKD1L1	ENST00000686775.1	c.375+1092T>G		intron_variant	Intron 4 of 15			ENSP00000508550.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.31
DANN	Benign	0.76
PhyloP100		-0.92

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: rs921634; hg19: chr7-47872845;