7-47796104-T-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L1	NM_138295.5	c.8240A>C	p.Gln2747Pro	missense_variant	Exon 55 of 57	ENST00000289672.7	NP_612152.1
PKD1L1	XM_017011798.3	c.8417A>C	p.Gln2806Pro	missense_variant	Exon 56 of 59		XP_016867287.1
PKD1L1-AS1	NR_161268.1	n.153+661T>G		intron_variant	Intron 1 of 2
PKD1L1-AS1	NR_161269.1	n.153+661T>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L1	ENST00000289672.7	c.8240A>C	p.Gln2747Pro	missense_variant	Exon 55 of 57	1	NM_138295.5	ENSP00000289672.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Jan 23, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.8240A>C (p.Q2747P) alteration is located in exon 55 (coding exon 55) of the PKD1L1 gene. This alteration results from a A to C substitution at nucleotide position 8240, causing the glutamine (Q) at amino acid position 2747 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-47835702;