6-51616527-ATTT-ATTTTTT

Variant names:

• chr6-51616527-A-ATTT
• rs113144792
• NM_138694.4:c.*2551_*2553dupAAA

Variant summary

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

The NM_138694.4(PKHD1):​c.*2551_*2553dupAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 360,994 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00034 (0 hom.)
• Consequence: PKHD1 NM_138694.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790

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]

ENSG00000228689 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKHD1	NM_138694.4	c.*2551_*2553dupAAA		3_prime_UTR_variant	Exon 67 of 67	ENST00000371117.8	NP_619639.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKHD1	ENST00000371117	c.*2551_*2553dupAAA		3_prime_UTR_variant	Exon 67 of 67	1	NM_138694.4	ENSP00000360158.3
ENSG00000228689	ENST00000454361.1	n.81-5815_81-5813dupTTT		intron_variant	Intron 1 of 1	3
ENSG00000228689	ENST00000589278.6	n.811-5820_811-5818dupTTT		intron_variant	Intron 2 of 2	5
ENSG00000228689	ENST00000650088.1	n.222-5815_222-5813dupTTT		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0000991 AC: 14 AN: 141240 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000520

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000214

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000691

Gnomad FIN AF: 0.000687

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000337 AC: 74 AN: 219754 Hom.: 0 Cov.: 0 AF XY: 0.000313 AC XY: 35 AN XY: 111736

Gnomad4 AFR exome AF: 0.000465

Gnomad4 AMR exome AF: 0.000596

Gnomad4 ASJ exome AF: 0.000243

Gnomad4 EAS exome AF: 0.000143

Gnomad4 SAS exome AF: 0.000971

Gnomad4 FIN exome AF: 0.000385

Gnomad4 NFE exome AF: 0.000354

Gnomad4 OTH exome AF: 0.000206

GnomAD4 genome AF: 0.0000991 AC: 14 AN: 141240 Hom.: 0 Cov.: 28 AF XY: 0.000146 AC XY: 10 AN XY: 68356

Gnomad4 AFR AF: 0.0000520

Gnomad4 AMR AF: 0.000214

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000691

Gnomad4 FIN AF: 0.000687

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs113144792; hg19: chr6-51481325;