NM_138694.4:c.*2551_*2553delAAA

Variant names:

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

Variant summary

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

The NM_138694.4(PKHD1):​c.*2551_*2553delAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000486 in 360,078 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 0.0000071 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00080 (0 hom.)
• Consequence: PKHD1 NM_138694.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276

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_*2553delAAA		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_*2553delAAA		3_prime_UTR_variant	Exon 67 of 67	1	NM_138694.4	ENSP00000360158.3
ENSG00000228689	ENST00000454361.1	n.81-5815_81-5813delTTT		intron_variant	Intron 1 of 1	3
ENSG00000228689	ENST00000589278.6	n.811-5820_811-5818delTTT		intron_variant	Intron 2 of 2	5
ENSG00000228689	ENST00000650088.1	n.222-5815_222-5813delTTT		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00000708 AC: 1 AN: 141228 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000260

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: 0.000795 AC: 174 AN: 218850 Hom.: 0 AF XY: 0.000755 AC XY: 84 AN XY: 111278

Gnomad4 AFR exome AF: 0.000779

Gnomad4 AMR exome AF: 0.000898

Gnomad4 ASJ exome AF: 0.000852

Gnomad4 EAS exome AF: 0.000764

Gnomad4 SAS exome AF: 0.00146

Gnomad4 FIN exome AF: 0.000829

Gnomad4 NFE exome AF: 0.000767

Gnomad4 OTH exome AF: 0.000897

GnomAD4 genome AF: 0.00000708 AC: 1 AN: 141228 Hom.: 0 Cov.: 28 AF XY: 0.0000146 AC XY: 1 AN XY: 68350

Gnomad4 AFR AF: 0.0000260

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs113144792; hg19: chr6-51481325;