14-55671640-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001079521.2(KTN1):​c.3423C>A​(p.Ser1141Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S1141S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KTN1 NM_001079521.2 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=-2.68 with no splicing effect.

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249254 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458580 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725620

African (AFR) AF: 0.00 AC: 0 AN: 33334

American (AMR) AF: 0.00 AC: 0 AN: 44456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26050

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39604

South Asian (SAS) AF: 0.00 AC: 0 AN: 85664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110074

Other (OTH) AF: 0.00 AC: 0 AN: 60266

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	1.7
DANN	Benign	0.55
PhyloP100		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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;