14-55671640-C-T

Variant names:

• chr14-55671640-C-T
• rs41304375
• NM_001079521.2:c.3423C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.68
• Publications: 7 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 -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 VariationId 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

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.3423C>T	p.Ser1141Ser	synonymous	Exon 36 of 44	NP_001072989.1	Q86UP2-1
	KTN1	NM_001402682.1		c.3423C>T	p.Ser1141Ser	synonymous	Exon 37 of 45	NP_001389611.1	Q86UP2-1
	KTN1	NM_001402683.1		c.3354C>T	p.Ser1118Ser	synonymous	Exon 35 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.3423C>T	p.Ser1141Ser	synonymous	Exon 36 of 44	ENSP00000378725.3	Q86UP2-1
	KTN1	ENST00000395308.5	TSL:1	c.3354C>T	p.Ser1118Ser	synonymous	Exon 36 of 43	ENSP00000378719.1	Q86UP2-3
	KTN1	ENST00000395311.5	TSL:1	c.3354C>T	p.Ser1118Ser	synonymous	Exon 35 of 42	ENSP00000378722.1	Q86UP2-3

Frequencies

GnomAD3 genomes AF: 0.00773 AC: 1176 AN: 152076 Hom.: 7 Cov.: 32

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

GnomAD2 exomes AF: 0.00878 AC: 2188 AN: 249254 AF XY: 0.00917

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 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.: 29 AF XY: 0.0108 AC XY: 7848 AN XY: 725552

African (AFR) AF: 0.00174 AC: 58 AN: 33334

American (AMR) AF: 0.00538 AC: 239 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.0134 AC: 350 AN: 26046

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39604

South Asian (SAS) AF: 0.00563 AC: 482 AN: 85660

European-Finnish (FIN) AF: 0.00787 AC: 420 AN: 53378

Middle Eastern (MID) AF: 0.00834 AC: 48 AN: 5754

European-Non Finnish (NFE) AF: 0.0124 AC: 13710 AN: 1109936

Other (OTH) AF: 0.0103 AC: 621 AN: 60258

GnomAD4 genome AF: 0.00773 AC: 1176 AN: 152194 Hom.: 7 Cov.: 32 AF XY: 0.00722 AC XY: 537 AN XY: 74422

African (AFR) AF: 0.00214 AC: 89 AN: 41538

American (AMR) AF: 0.00648 AC: 99 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4822

European-Finnish (FIN) AF: 0.00755 AC: 80 AN: 10600

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0119 AC: 812 AN: 67990

Other (OTH) AF: 0.00992 AC: 21 AN: 2116

Alfa AF: 0.0104 Hom.: 4

Bravo AF: 0.00736

Asia WGS AF: 0.00202 AC: 7 AN: 3476

EpiCase AF: 0.0119

EpiControl AF: 0.0143

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	-0.54
CADD	Benign	5.9
DANN	Benign	0.54
PhyloP100		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs41304375; hg19: chr14-56138358; COSMIC: COSV58540282; COSMIC: COSV58540282;