NM_138295.5:c.8240A>C

Variant names:

• chr7-47796104-T-G
• NM_138295.5:c.8240A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138295.5(PKD1L1):​c.8240A>C​(p.Gln2747Pro) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PKD1L1 NM_138295.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.24
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11065808).

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.8240A>C	p.Gln2747Pro	missense	Exon 55 of 57	NP_612152.1	Q8TDX9-1
	PKD1L1-AS1	NR_161268.1		n.153+661T>G		intron	N/A
	PKD1L1-AS1	NR_161269.1		n.153+661T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L1	ENST00000289672.7	TSL:1 MANE Select	c.8240A>C	p.Gln2747Pro	missense	Exon 55 of 57	ENSP00000289672.2	Q8TDX9-1
	PKD1L1-AS1	ENST00000623971.3	TSL:1	n.153+661T>G		intron	N/A
	PKD1L1	ENST00000690269.1		c.8240A>C	p.Gln2747Pro	missense	Exon 55 of 58	ENSP00000510743.1	A0A8I5KWV8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.9
DANN	Benign	0.94
DEOGEN2	Benign	0.25	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.2
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.036
Sift	Benign	0.064	T
Sift4G	Uncertain	0.023	D
Polyphen		0.015	B
Vest4		0.17
MutPred		0.53		Gain of glycosylation at Q2747 (P = 0.0131)
MVP		0.56
MPC		0.11
ClinPred		0.085	T
GERP RS		-0.84
Varity_R		0.28
gMVP		0.22
Mutation Taster		=96/4	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

hg19: chr7-47835702;