rs11172254

Positions:

• chr12-57574955-G-A
• chr12-57574955-G-T

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.1717-129G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 801,012 control chromosomes in the GnomAD database, including 122,824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (18837 hom., cov: 31)
  • Exomes 𝑓: 0.55 (103987 hom.)
• Consequence: KIF5A NM_004984.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.753

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]

KIF5A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 12-57574955-G-A is Benign according to our data. Variant chr12-57574955-G-A is described in ClinVar as [Benign]. Clinvar id is 682853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF5A	NM_004984.4	c.1717-129G>A		intron_variant		ENST00000455537.7	NP_004975.2
KIF5A	NM_001354705.2	c.1450-129G>A		intron_variant			NP_001341634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF5A	ENST00000455537.7	c.1717-129G>A		intron_variant		1	NM_004984.4	ENSP00000408979.2

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69944 AN: 151924 Hom.: 18846 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.518

GnomAD4 exome AF: 0.550 AC: 356700 AN: 648970 Hom.: 103987 AF XY: 0.547 AC XY: 188468 AN XY: 344808

Gnomad4 AFR exome AF: 0.177

Gnomad4 AMR exome AF: 0.470

Gnomad4 ASJ exome AF: 0.608

Gnomad4 EAS exome AF: 0.209

Gnomad4 SAS exome AF: 0.411

Gnomad4 FIN exome AF: 0.485

Gnomad4 NFE exome AF: 0.627

Gnomad4 OTH exome AF: 0.537

GnomAD4 genome AF: 0.460 AC: 69922 AN: 152042 Hom.: 18837 Cov.: 31 AF XY: 0.452 AC XY: 33550 AN XY: 74286

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.513

Alfa AF: 0.585 Hom.: 35169

Bravo AF: 0.450

Asia WGS AF: 0.312 AC: 1086 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	clinical testing	GeneDx	Jun 14, 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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.71
DANN	Benign	0.65

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: rs11172254; hg19: chr12-57968738; COSMIC: COSV54055337;