rs547684666

Variant names:

• chr7-47796098-T-A
• rs547684666
• NM_138295.5:c.8246A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-47796098-T-A
• chr7-47796098-T-C
• chr7-47796098-T-G

Variant summary

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

The NM_138295.5(PKD1L1):​c.8246A>T​(p.Lys2749Ile) 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. 14/22 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. K2749T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PKD1L1 NM_138295.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• 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=0.33053708).

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.8246A>T	p.Lys2749Ile	missense	Exon 55 of 57	NP_612152.1	Q8TDX9-1
	PKD1L1-AS1	NR_161268.1		n.153+655T>A		intron	N/A
	PKD1L1-AS1	NR_161269.1		n.153+655T>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.8246A>T	p.Lys2749Ile	missense	Exon 55 of 57	ENSP00000289672.2	Q8TDX9-1
	PKD1L1-AS1	ENST00000623971.3	TSL:1	n.153+655T>A		intron	N/A
	PKD1L1	ENST00000690269.1		c.8246A>T	p.Lys2749Ile	missense	Exon 55 of 58	ENSP00000510743.1	A0A8I5KWV8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.2
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.076
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.011	D
Polyphen		0.99	D
Vest4		0.21
MutPred		0.53		Loss of solvent accessibility (P = 7e-04)
MVP		0.89
MPC		0.61
ClinPred		0.86	D
GERP RS		3.1
Varity_R		0.35
gMVP		0.27
Mutation Taster		=100/0	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: rs547684666; hg19: chr7-47835696;