rs3756754

Variant names:

• chr5-132737787-G-A
• rs3756754
• NM_001300791.2:c.-368C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-132737787-G-A
• chr5-132737787-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001300791.2(KIF3A):​c.-368C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 386,054 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00092 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (12 hom.)
• Consequence: KIF3A NM_001300791.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000919 (140/152390) while in subpopulation EAS AF= 0.0254 (132/5192). AF 95% confidence interval is 0.0219. There are 1 homozygotes in gnomad4. There are 85 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 140 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF3A	NM_001300791.2	c.-368C>T		upstream_gene_variant		ENST00000403231.6	NP_001287720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF3A	ENST00000403231.6	c.-368C>T		upstream_gene_variant		2	NM_001300791.2	ENSP00000385808.1
KIF3A	ENST00000378735.5	c.-368C>T		upstream_gene_variant		1		ENSP00000368009.1
KIF3A	ENST00000618515.4	c.-368C>T		upstream_gene_variant		5		ENSP00000483023.1
KIF3A	ENST00000378746.8	c.-368C>T		upstream_gene_variant		5		ENSP00000368020.3

Frequencies

GnomAD3 genomes AF: 0.000926 AC: 141 AN: 152272 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000955

GnomAD4 exome AF: 0.00226 AC: 529 AN: 233664 Hom.: 12 AF XY: 0.00200 AC XY: 239 AN XY: 119368

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0264

Gnomad4 SAS exome AF: 0.000243

Gnomad4 FIN exome AF: 0.000103

Gnomad4 NFE exome AF: 0.0000471

Gnomad4 OTH exome AF: 0.000839

GnomAD4 genome AF: 0.000919 AC: 140 AN: 152390 Hom.: 1 Cov.: 33 AF XY: 0.00114 AC XY: 85 AN XY: 74522

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0254

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.000277 Hom.: 0

Bravo AF: 0.00130

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3756754; hg19: chr5-132073479;