rs566540835

Variant names:

• chr6-51830998-TA-T
• rs566540835
• NM_138694.4:c.8174-10delT

Your query was ambiguous. Multiple possible variants found:

• chr6-51830998-TA-T
• chr6-51830998-TA-TAA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_138694.4(PKHD1):​c.8174-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000767 in 1,603,912 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000084 (0 hom.)
• Consequence: PKHD1 NM_138694.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 2.74

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 6-51830998-TA-T is Benign according to our data. Variant chr6-51830998-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 706495.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKHD1	NM_138694.4	c.8174-10delT		intron_variant	Intron 51 of 66	ENST00000371117.8	NP_619639.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKHD1	ENST00000371117.8	c.8174-10delT		intron_variant	Intron 51 of 66	1	NM_138694.4	ENSP00000360158.3
PKHD1	ENST00000340994.4	c.8174-10delT		intron_variant	Intron 51 of 60	5		ENSP00000341097.4

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151716 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000840 AC: 122 AN: 1452196 Hom.: 0 Cov.: 29 AF XY: 0.0000719 AC XY: 52 AN XY: 722760

Gnomad4 AFR exome AF: 0.0000905

Gnomad4 AMR exome AF: 0.0000225

Gnomad4 ASJ exome AF: 0.0000385

Gnomad4 EAS exome AF: 0.000152

Gnomad4 SAS exome AF: 0.0000465

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.0000878

Gnomad4 OTH exome AF: 0.000150

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151716 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74068

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal recessive polycystic kidney disease Benign:1

Jan 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PKHD1-related disorder Benign:1

Nov 04, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs566540835; hg19: chr6-51695796;