chr14-55661569-A-G

Variant names:

• chr14-55661569-A-G
• rs149795430
• NM_001079521.2:c.3047A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001079521.2(KTN1):​c.3047A>G​(p.Asp1016Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0002 in 1,604,708 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (1 hom.)
• Consequence: KTN1 NM_001079521.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.378
• Publications: 1 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038861334).
• BP6: Variant 14-55661569-A-G is Benign according to our data. Variant chr14-55661569-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 736860.Status of the report is criteria_provided_single_submitter, 1 stars.

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.3047A>G	p.Asp1016Gly	missense	Exon 32 of 44	NP_001072989.1	Q86UP2-1
	KTN1	NM_001402682.1		c.3047A>G	p.Asp1016Gly	missense	Exon 33 of 45	NP_001389611.1	Q86UP2-1
	KTN1	NM_001402683.1		c.2978A>G	p.Asp993Gly	missense	Exon 31 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.3047A>G	p.Asp1016Gly	missense	Exon 32 of 44	ENSP00000378725.3	Q86UP2-1
	KTN1	ENST00000395308.5	TSL:1	c.2978A>G	p.Asp993Gly	missense	Exon 32 of 43	ENSP00000378719.1	Q86UP2-3
	KTN1	ENST00000395311.5	TSL:1	c.2978A>G	p.Asp993Gly	missense	Exon 31 of 42	ENSP00000378722.1	Q86UP2-3

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 166 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00374

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000260 AC: 65 AN: 250236 AF XY: 0.000170

Gnomad AFR exome AF: 0.00388

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000107 AC: 155 AN: 1452380 Hom.: 1 Cov.: 26 AF XY: 0.0000830 AC XY: 60 AN XY: 723204

African (AFR) AF: 0.00420 AC: 140 AN: 33298

American (AMR) AF: 0.0000672 AC: 3 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39476

South Asian (SAS) AF: 0.00 AC: 0 AN: 85882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103860

Other (OTH) AF: 0.000183 AC: 11 AN: 60060

GnomAD4 genome AF: 0.00109 AC: 166 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.000926 AC XY: 69 AN XY: 74480

African (AFR) AF: 0.00373 AC: 155 AN: 41580

American (AMR) AF: 0.000327 AC: 5 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000519 Hom.: 1

Bravo AF: 0.00125

ESP6500AA AF: 0.00363 AC: 16

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000321 AC: 39

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.29	N
PhyloP100		0.38
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.032
Sift	Benign	0.36	T
Sift4G	Benign	0.22	T
Polyphen		0.052	B
Vest4		0.10
MVP		0.33
MPC		0.042
ClinPred		0.013	T
GERP RS		0.64
PromoterAI		0.0046	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.052
gMVP		0.12
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs149795430; hg19: chr14-56128287;