7-47800653-C-A

Variant names:

• chr7-47800653-C-A
• rs763504220
• NM_138295.5:c.8189G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138295.5(PKD1L1):​c.8189G>T​(p.Gly2730Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G2730E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PKD1L1 NM_138295.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.381
• Publications: 0 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-AS1 (HGNC:21911): (PKD1L1 antisense RNA 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35166132).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L1	NM_138295.5	MANE Select	c.8189G>T	p.Gly2730Val	missense	Exon 54 of 57	NP_612152.1	Q8TDX9-1
	PKD1L1-AS1	NR_161268.1		n.153+5210C>A		intron	N/A
	PKD1L1-AS1	NR_161269.1		n.153+5210C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L1	ENST00000289672.7	TSL:1 MANE Select	c.8189G>T	p.Gly2730Val	missense	Exon 54 of 57	ENSP00000289672.2	Q8TDX9-1
	PKD1L1-AS1	ENST00000623971.3	TSL:1	n.153+5210C>A		intron	N/A
	PKD1L1	ENST00000690269.1		c.8189G>T	p.Gly2730Val	missense	Exon 54 of 58	ENSP00000510743.1	A0A8I5KWV8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251228 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: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461430 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727060

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111600

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.77
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.38
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.13
Sift	Benign	0.26	T
Sift4G	Benign	0.39	T
Polyphen		0.94	P
Vest4		0.24
MutPred		0.68		Loss of methylation at R2733 (P = 0.0827)
MVP		0.66
MPC		0.27
ClinPred		0.27	T
GERP RS		2.8
Varity_R		0.14
gMVP		0.17
Mutation Taster		=93/7	polymorphism

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: rs763504220; hg19: chr7-47840251;