12-57585407-C-G

Position:

• chr12-57585407-C-G

Variant summary

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

The NM_004984.4(KIF5A):​c.*1226C>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 0.26 in 154,312 control chromosomes in the GnomAD database, including 6,394 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 0.26 (6316 hom., cov: 32)
  • Exomes 𝑓: 0.24 (78 hom.)
• Consequence: KIF5A NM_004984.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF5A	NM_004984.4	c.*1226C>G		3_prime_UTR_variant	29/29	ENST00000455537.7	NP_004975.2
KIF5A	NM_001354705.2	c.*1226C>G		3_prime_UTR_variant	26/26		NP_001341634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF5A	ENST00000455537.7	c.*1226C>G		3_prime_UTR_variant	29/29	1	NM_004984.4	ENSP00000408979	P1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39479 AN: 151956 Hom.: 6292 Cov.: 32

Gnomad AFR AF: 0.0931

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.265

GnomAD4 exome AF: 0.243 AC: 543 AN: 2236 Hom.: 78 Cov.: 0 AF XY: 0.247 AC XY: 278 AN XY: 1126

Gnomad4 AFR exome AF: 0.0395

Gnomad4 AMR exome AF: 0.625

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.469

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.326

GnomAD4 genome AF: 0.260 AC: 39526 AN: 152076 Hom.: 6316 Cov.: 32 AF XY: 0.272 AC XY: 20205 AN XY: 74342

Gnomad4 AFR AF: 0.0929

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.272

Alfa AF: 0.162 Hom.: 368

Bravo AF: 0.253

Asia WGS AF: 0.490 AC: 1704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.88
DANN	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1678536; hg19: chr12-57979190;