chr6-52079950-G-C

Position:

• chr6-52079950-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138694.4(PKHD1):​c.340C>G​(p.Gln114Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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: 32)
• Consequence: PKHD1 NM_138694.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.29

Genes affected

PKHD1 (HGNC:9016): (PKHD1 ciliary IPT domain containing fibrocystin/polyductin) The protein encoded by this gene is predicted to have a single transmembrane (TM)-spanning domain and multiple copies of an immunoglobulin-like plexin-transcription-factor domain. Alternative splicing results in two transcript variants encoding different isoforms. Other alternatively spliced transcripts have been described, but the full length sequences have not been determined. Several of these transcripts are predicted to encode truncated products which lack the TM and may be secreted. Mutations in this gene cause autosomal recessive polycystic kidney disease, also known as polycystic kidney and hepatic disease-1. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40601295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKHD1	NM_138694.4	c.340C>G	p.Gln114Glu	missense_variant	5/67	ENST00000371117.8	NP_619639.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKHD1	ENST00000371117.8	c.340C>G	p.Gln114Glu	missense_variant	5/67	1	NM_138694.4	ENSP00000360158.3
PKHD1	ENST00000340994.4	c.340C>G	p.Gln114Glu	missense_variant	5/61	5		ENSP00000341097.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	17
DANN	Benign	0.50
DEOGEN2	Benign	0.20	T;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.49	T;T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.29
Sift	Uncertain	0.028	D;T
Sift4G	Benign	0.30	T;T
Polyphen		0.90	P;B
Vest4		0.44
MutPred		0.43		Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);
MVP		0.97
MPC		0.074
ClinPred		0.38	T
GERP RS		5.3
Varity_R		0.18
gMVP		0.46

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: chr6-51944748;