3-44794237-G-T

Position:

• chr3-44794237-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000326047.9(KIF15):​c.660G>T​(p.Arg220Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KIF15 ENST00000326047.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.341

Genes affected

KIF15 (HGNC:17273): (kinesin family member 15) Predicted to enable microtubule binding activity and microtubule motor activity. Predicted to be involved in microtubule-based movement. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40897366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF15	NM_020242.3	c.660G>T	p.Arg220Ser	missense_variant	8/35	ENST00000326047.9	NP_064627.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF15	ENST00000326047.9	c.660G>T	p.Arg220Ser	missense_variant	8/35	1	NM_020242.3	ENSP00000324020	P1
KIF15	ENST00000438321.5	c.*365G>T		3_prime_UTR_variant, NMD_transcript_variant	7/34	1		ENSP00000406939
KIF15	ENST00000481166.6	c.-25G>T		5_prime_UTR_variant	3/18	5		ENSP00000425499

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461336 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726936

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

AiLife Diagnostics, AiLife Diagnostics

Jul 18, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.81	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.26	N
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.34
Sift	Benign	0.066	T
Sift4G	Benign	0.32	T
Polyphen		0.060	B
Vest4		0.80
MutPred		0.49		Loss of MoRF binding (P = 0.0336);
MVP		0.47
MPC		0.45
ClinPred		0.61	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.64
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-44835729;