Genetic Variant KTN1:p.Ser597Ser (chr14-55639190-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001079521.2(KTN1):c.1791C>T(p.Ser597Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00578 in 1,602,384 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0091 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 55 hom. )

Consequence

KTN1
NM_001079521.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.55

Variant links:

Genes affected

KTN1 (HGNC:6467): (kinectin 1) This gene encodes an integral membrane protein that is a member of the kinectin protein family. The encoded protein is primarily localized to the endoplasmic reticulum membrane. This protein binds kinesin and may be involved in intracellular organelle motility. This protein also binds translation elongation factor-delta and may be involved in the assembly of the elongation factor-1 complex. Alternate splicing results in multiple transcript variants of this gene. [provided by RefSeq, Aug 2012]

KTN1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 14-55639190-C-T is Benign according to our data. Variant chr14-55639190-C-T is described in ClinVar as [Benign]. Clinvar id is 710034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.55 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00913 (1385/151726) while in subpopulation SAS AF= 0.0247 (119/4820). AF 95% confidence interval is 0.0211. There are 9 homozygotes in gnomad4. There are 685 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KTN1	NM_001079521.2 link	c.1791C>T	p.Ser597Ser	synonymous_variant	Exon 13 of 44	ENST00000395314.8	NP_001072989.1	Q86UP2-1A0A024R663

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KTN1	ENST00000395314.8 link	c.1791C>T	p.Ser597Ser	synonymous_variant	Exon 13 of 44	1	NM_001079521.2	ENSP00000378725.3		Q86UP2-1

Frequencies

GnomAD3 genomes

AF:

0.00903

AC:

1369

AN:

151608

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0178

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00572

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.0243

Gnomad FIN

AF:

0.00926

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00415

Gnomad OTH

AF:

0.00721

GnomAD3 exomes

AF:

0.00726

AC:

1813

AN:

249820

Hom.:

AF XY:

0.00760

AC XY:

1026

AN XY:

135074

show subpopulations

Gnomad AFR exome

AF:

0.0184

Gnomad AMR exome

AF:

0.00401

Gnomad ASJ exome

AF:

0.00150

Gnomad EAS exome

AF:

0.00153

Gnomad SAS exome

AF:

0.0195

Gnomad FIN exome

AF:

0.00848

Gnomad NFE exome

AF:

0.00453

Gnomad OTH exome

AF:

0.00754

GnomAD4 exome

AF:

0.00543

AC:

7883

AN:

1450658

Hom.:

Cov.:

AF XY:

0.00581

AC XY:

4195

AN XY:

722202

show subpopulations

Gnomad4 AFR exome

AF:

0.0202

Gnomad4 AMR exome

AF:

0.00428

Gnomad4 ASJ exome

AF:

0.000925

Gnomad4 EAS exome

AF:

0.000911

Gnomad4 SAS exome

AF:

0.0188

Gnomad4 FIN exome

AF:

0.00810

Gnomad4 NFE exome

AF:

0.00395

Gnomad4 OTH exome

AF:

0.00847

GnomAD4 genome

AF:

0.00913

AC:

1385

AN:

151726

Hom.:

Cov.:

AF XY:

0.00923

AC XY:

685

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.0179

Gnomad4 AMR

AF:

0.00571

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.0247

Gnomad4 FIN

AF:

0.00926

Gnomad4 NFE

AF:

0.00415

Gnomad4 OTH

AF:

0.0124

Alfa

AF:

0.00594

Hom.:

Bravo

AF:

0.00934

Asia WGS

AF:

0.0310

AC:

106

AN:

3472

EpiCase

AF:

0.00505

EpiControl

AF:

0.00505

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.50

CADD

Benign

8.4

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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