chr5-132703040-T-C

Variant names:

• chr5-132703040-T-C
• rs759731870
• NM_001300791.2:c.1492A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001300791.2(KIF3A):​c.1492A>G​(p.Lys498Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000385 in 1,612,034 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: KIF3A NM_001300791.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02
• Publications: 0 publications found

Genes affected

KIF3A (HGNC:6319): (kinesin family member 3A) Enables protein phosphatase binding activity; small GTPase binding activity; and spectrin binding activity. Involved in protein localization to cell junction and protein transport. Located in centriole and centrosome. Part of kinesin II complex. Colocalizes with spindle microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000230612 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 58 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300791.2. 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
	KIF3A	NM_001300791.2	MANE Select	c.1492A>G	p.Lys498Glu	missense	Exon 13 of 19	NP_001287720.1	E9PES4
	KIF3A	NM_001300792.2		c.1420A>G	p.Lys474Glu	missense	Exon 12 of 18	NP_001287721.1	J3KPF9
	KIF3A	NM_007054.7		c.1411A>G	p.Lys471Glu	missense	Exon 11 of 17	NP_008985.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF3A	ENST00000403231.6	TSL:2 MANE Select	c.1492A>G	p.Lys498Glu	missense	Exon 13 of 19	ENSP00000385808.1	E9PES4
	KIF3A	ENST00000378735.5	TSL:1	c.1420A>G	p.Lys474Glu	missense	Exon 12 of 18	ENSP00000368009.1	J3KPF9
	KIF3A	ENST00000618515.4	TSL:5	c.1489A>G	p.Lys497Glu	missense	Exon 13 of 19	ENSP00000483023.1	A0A087X011

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000441

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.00000802 AC: 2 AN: 249506 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000397 AC: 58 AN: 1459840 Hom.: 0 Cov.: 31 AF XY: 0.0000441 AC XY: 32 AN XY: 726210

African (AFR) AF: 0.0000300 AC: 1 AN: 33378

American (AMR) AF: 0.00 AC: 0 AN: 44282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39614

South Asian (SAS) AF: 0.00 AC: 0 AN: 85730

European-Finnish (FIN) AF: 0.0000376 AC: 2 AN: 53154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000486 AC: 54 AN: 1111474

Other (OTH) AF: 0.0000166 AC: 1 AN: 60334

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68008

Other (OTH) AF: 0.000480 AC: 1 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.69	D
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Uncertain	0.32	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		8.0
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.58	P
Vest4		0.65
MutPred		0.27		Loss of ubiquitination at K498 (P = 0.0047)
MVP		0.57
MPC		1.3
ClinPred		0.84	D
GERP RS		6.1
PromoterAI		0.019	Neutral
Varity_R		0.69
gMVP		0.69
Mutation Taster		=30/70	disease causing

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: rs759731870; hg19: chr5-132038732;