NM_138295.5:c.*212C>T

Variant names:

• chr7-47774931-G-A
• rs17545279
• NM_138295.5:c.*212C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_138295.5(PKD1L1):​c.*212C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 585,100 control chromosomes in the GnomAD database, including 6,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1457 hom., cov: 33)
  • Exomes 𝑓: 0.14 (4786 hom.)
• Consequence: PKD1L1 NM_138295.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.45

Genes affected

PKD1L1 (HGNC:18053): (polycystin 1 like 1, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family containing 11 transmembrane domains, a receptor for egg jelly (REJ) domain, and a polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain. The encoded protein may play a role in the male reproductive system. Alternative splice variants have been described but their biological nature has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-47774931-G-A is Benign according to our data. Variant chr7-47774931-G-A is described in ClinVar as [Benign]. Clinvar id is 1179665.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L1	NM_138295.5	c.*212C>T		3_prime_UTR_variant	Exon 57 of 57	ENST00000289672.7	NP_612152.1
PKD1L1	XM_017011798.3	c.*212C>T		3_prime_UTR_variant	Exon 59 of 59		XP_016867287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L1	ENST00000289672	c.*212C>T		3_prime_UTR_variant	Exon 57 of 57	1	NM_138295.5	ENSP00000289672.2
PKD1L1	ENST00000690269	c.*212C>T		3_prime_UTR_variant	Exon 58 of 58			ENSP00000510743.1
PKD1L1	ENST00000685709	c.*212C>T		3_prime_UTR_variant	Exon 56 of 56			ENSP00000509540.1
PKD1L1	ENST00000648482.1	c.1158+17696C>T		intron_variant	Intron 7 of 7			ENSP00000496786.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19664 AN: 152048 Hom.: 1454 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.0997

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.137 AC: 59478 AN: 432934 Hom.: 4786 Cov.: 5 AF XY: 0.138 AC XY: 31586 AN XY: 229678

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.0861

Gnomad4 ASJ exome AF: 0.135

Gnomad4 EAS exome AF: 0.0264

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.252

Gnomad4 NFE exome AF: 0.141

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.129 AC: 19684 AN: 152166 Hom.: 1457 Cov.: 33 AF XY: 0.135 AC XY: 10029 AN XY: 74388

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0998

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.119

Alfa AF: 0.133 Hom.: 584

Bravo AF: 0.115

Asia WGS AF: 0.0600 AC: 208 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.2
DANN	Benign	0.55

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: rs17545279; hg19: chr7-47814529;