5-132703073-T-C

Variant names:

• chr5-132703073-T-C
• rs374997234
• NM_001300791.2:c.1467-8A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001300791.2(KIF3A):​c.1467-8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIF3A NM_001300791.2 splice_region, intron
• Scores: Splicing: ADA: 0.9991
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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.1467-8A>G		splice_region intron	N/A	NP_001287720.1	E9PES4
	KIF3A	NM_001300792.2		c.1395-8A>G		splice_region intron	N/A	NP_001287721.1	J3KPF9
	KIF3A	NM_007054.7		c.1386-8A>G		splice_region 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.1467-8A>G		splice_region intron	N/A	ENSP00000385808.1	E9PES4
	KIF3A	ENST00000378735.5	TSL:1	c.1395-8A>G		splice_region intron	N/A	ENSP00000368009.1	J3KPF9
	KIF3A	ENST00000618515.4	TSL:5	c.1464-8A>G		splice_region intron	N/A	ENSP00000483023.1	A0A087X011

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	24
DANN	Benign	0.83
PhyloP100		2.0
PromoterAI		0.0011	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.95
SpliceAI score (max)		0.99		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.99		Position offset: -1
DS_AL_spliceai		0.41		Position offset: -8

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

Other links and lift over

dbSNP: rs374997234; hg19: chr5-132038765;