rs199700485

Variant names:

• chr16-2104530-G-C
• NM_001009944.3:c.8129C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-2104530-G-C
• chr16-2104530-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM5 PP3

The NM_001009944.3(PKD1):​c.8129C>G​(p.Thr2710Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,417,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. T2710N) has been classified as Likely pathogenic.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PKD1 NM_001009944.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.21

Genes affected

PKD1 (HGNC:9008): (polycystin 1, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family. The encoded glycoprotein contains a large N-terminal extracellular region, multiple transmembrane domains and a cytoplasmic C-tail. It is an integral membrane protein that functions as a regulator of calcium permeable cation channels and intracellular calcium homoeostasis. It is also involved in cell-cell/matrix interactions and may modulate G-protein-coupled signal-transduction pathways. It plays a role in renal tubular development, and mutations in this gene cause autosomal dominant polycystic kidney disease type 1 (ADPKD1). ADPKD1 is characterized by the growth of fluid-filled cysts that replace normal renal tissue and result in end-stage renal failure. Splice variants encoding different isoforms have been noted for this gene. Also, six pseudogenes, closely linked in a known duplicated region on chromosome 16p, have been described. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr16-2104530-G-T is described in Lovd as [Likely_pathogenic].
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.781

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3	c.8129C>G	p.Thr2710Ser	missense_variant	Exon 22 of 46	ENST00000262304.9	NP_001009944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1	ENST00000262304.9	c.8129C>G	p.Thr2710Ser	missense_variant	Exon 22 of 46	1	NM_001009944.3	ENSP00000262304.4

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1417340 Hom.: 0 Cov.: 30 AF XY: 0.00000284 AC XY: 2 AN XY: 703066

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.19e-7

Gnomad4 OTH exome AF: 0.0000171

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T;.
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.75	T;T
M_CAP	Pathogenic	0.88	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.19
Sift	Uncertain	0.011	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.47
MutPred		0.28		Loss of helix (P = 0.028);Loss of helix (P = 0.028);
MVP		0.89
ClinPred		0.91	D
GERP RS		3.3
Varity_R		0.16
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr16-2154531;