13-33061698-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004795.4(KL):c.2619T>C(p.Asn873Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 1,613,994 control chromosomes in the GnomAD database, including 799,606 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.97 ( 72414 hom., cov: 31)

Exomes 𝑓: 1.0 ( 727192 hom. )

Consequence

KL
NM_004795.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.231

Variant links:

Genes affected

KL (HGNC:6344): (klotho) This gene encodes a type-I membrane protein that is related to beta-glucosidases. Reduced production of this protein has been observed in patients with chronic renal failure (CRF), and this may be one of the factors underlying the degenerative processes (e.g., arteriosclerosis, osteoporosis, and skin atrophy) seen in CRF. Also, mutations within this protein have been associated with ageing and bone loss. [provided by RefSeq, Jul 2008]

KL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 13-33061698-T-C is Benign according to our data. Variant chr13-33061698-T-C is described in ClinVar as [Benign]. Clinvar id is 311705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-33061698-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.231 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KL	NM_004795.4 link	c.2619T>C	p.Asn873Asn	synonymous_variant	Exon 4 of 5	ENST00000380099.4	NP_004786.2	Q9UEF7-1
KL	XM_006719895.3 link	c.1698T>C	p.Asn566Asn	synonymous_variant	Exon 4 of 5		XP_006719958.1
KL	XM_047430776.1 link	c.*1019T>C		downstream_gene_variant			XP_047286732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KL	ENST00000380099.4 link	c.2619T>C	p.Asn873Asn	synonymous_variant	Exon 4 of 5	1	NM_004795.4	ENSP00000369442.3		Q9UEF7-1
KL	ENST00000487852.1 link	n.2677T>C		non_coding_transcript_exon_variant	Exon 4 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.974

AC:

148257

AN:

152138

Hom.:

72357

Cov.:

show subpopulations

Gnomad AFR

AF:

0.912

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.988

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.983

GnomAD3 exomes

AF:

0.994

AC:

249797

AN:

251402

Hom.:

124150

AF XY:

0.995

AC XY:

135242

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.914

Gnomad AMR exome

AF:

0.996

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.997

GnomAD4 exome

AF:

0.997

AC:

1457932

AN:

1461738

Hom.:

727192

Cov.:

AF XY:

0.998

AC XY:

725542

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.912

Gnomad4 AMR exome

AF:

0.994

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.994

GnomAD4 genome

AF:

0.974

AC:

148373

AN:

152256

Hom.:

72414

Cov.:

AF XY:

0.976

AC XY:

72647

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.912

Gnomad4 AMR

AF:

0.988

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.983

Alfa

AF:

0.993

Hom.:

77656

Bravo

AF:

0.970

Asia WGS

AF:

0.995

AC:

3461

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

1.00

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Tumoral calcinosis, hyperphosphatemic, familial, 3

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.061

DANN

Benign

0.29

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over