14-55639190-C-T

Variant names:

• chr14-55639190-C-T
• rs80214241
• NM_001079521.2:c.1791C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.55
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079521.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KTN1	NM_001079521.2	MANE Select	c.1791C>T	p.Ser597Ser	synonymous	Exon 13 of 44	NP_001072989.1	Q86UP2-1
	KTN1	NM_001402682.1		c.1791C>T	p.Ser597Ser	synonymous	Exon 14 of 45	NP_001389611.1	Q86UP2-1
	KTN1	NM_001402683.1		c.1791C>T	p.Ser597Ser	synonymous	Exon 13 of 43	NP_001389612.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KTN1	ENST00000395314.8	TSL:1 MANE Select	c.1791C>T	p.Ser597Ser	synonymous	Exon 13 of 44	ENSP00000378725.3	Q86UP2-1
	KTN1	ENST00000395308.5	TSL:1	c.1791C>T	p.Ser597Ser	synonymous	Exon 14 of 43	ENSP00000378719.1	Q86UP2-3
	KTN1	ENST00000395311.5	TSL:1	c.1791C>T	p.Ser597Ser	synonymous	Exon 13 of 42	ENSP00000378722.1	Q86UP2-3

Frequencies

GnomAD3 genomes AF: 0.00903 AC: 1369 AN: 151608 Hom.: 7 Cov.: 32

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

GnomAD2 exomes AF: 0.00726 AC: 1813 AN: 249820 AF XY: 0.00760

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 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.: 55 Cov.: 28 AF XY: 0.00581 AC XY: 4195 AN XY: 722202

African (AFR) AF: 0.0202 AC: 669 AN: 33150

American (AMR) AF: 0.00428 AC: 191 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.000925 AC: 24 AN: 25954

East Asian (EAS) AF: 0.000911 AC: 36 AN: 39522

South Asian (SAS) AF: 0.0188 AC: 1614 AN: 85750

European-Finnish (FIN) AF: 0.00810 AC: 432 AN: 53320

Middle Eastern (MID) AF: 0.0103 AC: 59 AN: 5740

European-Non Finnish (NFE) AF: 0.00395 AC: 4350 AN: 1102612

Other (OTH) AF: 0.00847 AC: 508 AN: 60010

GnomAD4 genome AF: 0.00913 AC: 1385 AN: 151726 Hom.: 9 Cov.: 32 AF XY: 0.00923 AC XY: 685 AN XY: 74178

African (AFR) AF: 0.0179 AC: 741 AN: 41464

American (AMR) AF: 0.00571 AC: 87 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3464

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5186

South Asian (SAS) AF: 0.0247 AC: 119 AN: 4820

European-Finnish (FIN) AF: 0.00926 AC: 98 AN: 10582

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00415 AC: 281 AN: 67662

Other (OTH) AF: 0.0124 AC: 26 AN: 2102

Alfa AF: 0.00608 Hom.: 5

Bravo AF: 0.00934

Asia WGS AF: 0.0310 AC: 106 AN: 3472

EpiCase AF: 0.00505

EpiControl AF: 0.00505

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.4
DANN	Benign	0.60
PhyloP100		-3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs80214241; hg19: chr14-56105908;