chr12-57582864-C-G

Position:

• chr12-57582864-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004984.4(KIF5A):​c.3020+235C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 638,542 control chromosomes in the GnomAD database, including 38,175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6970 hom., cov: 31)
  • Exomes 𝑓: 0.34 (31205 hom.)
• Consequence: KIF5A NM_004984.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.04

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-57582864-C-G is Benign according to our data. Variant chr12-57582864-C-G is described in ClinVar as [Benign]. Clinvar id is 682878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF5A	NM_004984.4	c.3020+235C>G		intron_variant		ENST00000455537.7
KIF5A	NM_001354705.2	c.2753+235C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF5A	ENST00000455537.7	c.3020+235C>G		intron_variant		1	NM_004984.4	P1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44131 AN: 151898 Hom.: 6966 Cov.: 31

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.338 AC: 164569 AN: 486526 Hom.: 31205 Cov.: 5 AF XY: 0.345 AC XY: 89366 AN XY: 259154

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.404

Gnomad4 ASJ exome AF: 0.294

Gnomad4 EAS exome AF: 0.656

Gnomad4 SAS exome AF: 0.476

Gnomad4 FIN exome AF: 0.354

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.314

GnomAD4 genome AF: 0.291 AC: 44162 AN: 152016 Hom.: 6970 Cov.: 31 AF XY: 0.298 AC XY: 22165 AN XY: 74280

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.270

Alfa AF: 0.293 Hom.: 873

Bravo AF: 0.284

Asia WGS AF: 0.507 AC: 1762 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.25
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2888334; hg19: chr12-57976647;