Genetic Variant KTN1:p.Ser1141Ser (chr14-55671640-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001079521.2(KTN1):c.3423C>T(p.Ser1141Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,610,618 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 7 hom., cov: 32)

Exomes 𝑓: 0.011 ( 109 hom. )

Consequence

KTN1
NM_001079521.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.68

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 14-55671640-C-T is Benign according to our data. Variant chr14-55671640-C-T is described in ClinVar as [Benign]. Clinvar id is 768655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.68 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KTN1	NM_001079521.2 link	c.3423C>T	p.Ser1141Ser	synonymous_variant	Exon 36 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.3423C>T	p.Ser1141Ser	synonymous_variant	Exon 36 of 44	1	NM_001079521.2	ENSP00000378725.3		Q86UP2-1

Frequencies

GnomAD3 genomes

AF:

0.00773

AC:

1176

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00649

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00601

Gnomad FIN

AF:

0.00755

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00878

AC:

2188

AN:

249254

Hom.:

AF XY:

0.00917

AC XY:

1234

AN XY:

134612

show subpopulations

Gnomad AFR exome

AF:

0.00234

Gnomad AMR exome

AF:

0.00539

Gnomad ASJ exome

AF:

0.0134

Gnomad EAS exome

AF:

0.000328

Gnomad SAS exome

AF:

0.00522

Gnomad FIN exome

AF:

0.00810

Gnomad NFE exome

AF:

0.0127

Gnomad OTH exome

AF:

0.00955

GnomAD4 exome

AF:

0.0109

AC:

15937

AN:

1458424

Hom.:

109

Cov.:

AF XY:

0.0108

AC XY:

7848

AN XY:

725552

show subpopulations

Gnomad4 AFR exome

AF:

0.00174

Gnomad4 AMR exome

AF:

0.00538

Gnomad4 ASJ exome

AF:

0.0134

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.00563

Gnomad4 FIN exome

AF:

0.00787

Gnomad4 NFE exome

AF:

0.0124

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.00773

AC:

1176

AN:

152194

Hom.:

Cov.:

AF XY:

0.00722

AC XY:

537

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00214

Gnomad4 AMR

AF:

0.00648

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00601

Gnomad4 FIN

AF:

0.00755

Gnomad4 NFE

AF:

0.0119

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.00736

Asia WGS

AF:

0.00202

AC:

AN:

3476

EpiCase

AF:

0.0119

EpiControl

AF:

0.0143

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

- -

Feb 25, 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

-0.54

CADD

Benign

5.9

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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