rs7313599

chr12-57585772-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004984.4(KIF5A):c.*1591A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 152,170 control chromosomes in the GnomAD database, including 8,909 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 0.32 (8907 hom., cov: 32)
  • Exomes 𝑓: 0.63 (2 hom.)
• Consequence: KIF5A NM_004984.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.12

Genes affected

KIF5A (HGNC:6323): (kinesin family member 5A) This gene encodes a member of the kinesin family of proteins. Members of this family are part of a multisubunit complex that functions as a microtubule motor in intracellular organelle transport. Mutations in this gene cause autosomal dominant spastic paraplegia 10. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF5A	NM_004984.4	c.*1591A>G		3_prime_UTR_variant	29/29	ENST00000455537.7
KIF5A	NM_001354705.2	c.*1591A>G		3_prime_UTR_variant	26/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF5A	ENST00000455537.7	c.*1591A>G		3_prime_UTR_variant	29/29	1	NM_004984.4	P1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49109 AN: 152044 Hom.: 8912 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.364

GnomAD4 exome AF: 0.625 AC: 5 AN: 8 Hom.: 2 Cov.: 0 AF XY: 0.667 AC XY: 4 AN XY: 6

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.833

GnomAD4 genome AF: 0.323 AC: 49100 AN: 152162 Hom.: 8907 Cov.: 32 AF XY: 0.315 AC XY: 23452 AN XY: 74404

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.359

Alfa AF: 0.415 Hom.: 12941

Bravo AF: 0.316

Asia WGS AF: 0.198 AC: 687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	12
Dann	Benign	0.74

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

LitVar

Other links and lift over

dbSNP: rs7313599; hg19: chr12-57979555;