5-132706454-C-T

Variant names:

• chr5-132706454-C-T
• rs3798130
• NM_001300791.2:c.1306G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001300791.2(KIF3A):​c.1306G>A​(p.Ala436Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,537,684 control chromosomes in the GnomAD database, including 44,181 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (10976 hom., cov: 32)
  • Exomes 𝑓: 0.18 (33205 hom.)
• Consequence: KIF3A NM_001300791.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• Publications: 25 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1507765E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

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.1306G>A	p.Ala436Thr	missense	Exon 11 of 19	NP_001287720.1	E9PES4
	KIF3A	NM_001300792.2		c.1234G>A	p.Ala412Thr	missense	Exon 10 of 18	NP_001287721.1	J3KPF9
	KIF3A	NM_007054.7		c.1229-2835G>A		intron	N/A	NP_008985.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF3A	ENST00000403231.6	TSL:2 MANE Select	c.1306G>A	p.Ala436Thr	missense	Exon 11 of 19	ENSP00000385808.1	E9PES4
	KIF3A	ENST00000378735.5	TSL:1	c.1234G>A	p.Ala412Thr	missense	Exon 10 of 18	ENSP00000368009.1	J3KPF9
	KIF3A	ENST00000618515.4	TSL:5	c.1303G>A	p.Ala435Thr	missense	Exon 11 of 19	ENSP00000483023.1	A0A087X011

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48761 AN: 151658 Hom.: 10946 Cov.: 32

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.257

GnomAD2 exomes AF: 0.270 AC: 38965 AN: 144268 AF XY: 0.251

Gnomad AFR exome AF: 0.572

Gnomad AMR exome AF: 0.415

Gnomad ASJ exome AF: 0.144

Gnomad EAS exome AF: 0.773

Gnomad FIN exome AF: 0.348

Gnomad NFE exome AF: 0.134

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.178 AC: 246750 AN: 1385908 Hom.: 33205 Cov.: 29 AF XY: 0.175 AC XY: 119803 AN XY: 683710

African (AFR) AF: 0.580 AC: 17881 AN: 30824

American (AMR) AF: 0.405 AC: 13787 AN: 34060

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 3619 AN: 25008

East Asian (EAS) AF: 0.716 AC: 24803 AN: 34654

South Asian (SAS) AF: 0.153 AC: 11848 AN: 77674

European-Finnish (FIN) AF: 0.341 AC: 16350 AN: 47894

Middle Eastern (MID) AF: 0.134 AC: 757 AN: 5666

European-Non Finnish (NFE) AF: 0.136 AC: 145498 AN: 1072640

Other (OTH) AF: 0.212 AC: 12207 AN: 57488

GnomAD4 genome AF: 0.322 AC: 48849 AN: 151776 Hom.: 10976 Cov.: 32 AF XY: 0.331 AC XY: 24534 AN XY: 74126

African (AFR) AF: 0.580 AC: 24036 AN: 41442

American (AMR) AF: 0.324 AC: 4951 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3468

East Asian (EAS) AF: 0.754 AC: 3901 AN: 5172

South Asian (SAS) AF: 0.182 AC: 876 AN: 4810

European-Finnish (FIN) AF: 0.357 AC: 3742 AN: 10480

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.151 AC: 10214 AN: 67844

Other (OTH) AF: 0.261 AC: 548 AN: 2100

Alfa AF: 0.198 Hom.: 19433

Bravo AF: 0.337

TwinsUK AF: 0.136 AC: 506

ALSPAC AF: 0.133 AC: 512

ExAC AF: 0.211 AC: 4292

Asia WGS AF: 0.459 AC: 1593 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Benign	0.93
DEOGEN2	Benign	0.098	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.060
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.95	T
PhyloP100		2.0
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.064
Sift	Benign	0.53	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.14
ClinPred		0.0066	T
GERP RS		3.6
gMVP		0.14
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs3798130; hg19: chr5-132042146; COSMIC: COSV66414258; COSMIC: COSV66414258;