12-57549925-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000676250.1(KIF5A):c.-25+3613A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00448 in 303,026 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0086 (21 hom., cov: 31)
  • Exomes 𝑓: 0.00030 (0 hom.)
• Consequence: KIF5A ENST00000676250.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.508

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 12-57549925-A-G is Benign according to our data. Variant chr12-57549925-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1201242.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00865 (1313/151806) while in subpopulation AFR AF= 0.0302 (1253/41422). AF 95% confidence interval is 0.0289. There are 21 homozygotes in gnomad4. There are 624 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 1309 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF5A	ENST00000676250.1	c.-25+3613A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00863 AC: 1309 AN: 151698 Hom.: 21 Cov.: 31

Gnomad AFR AF: 0.0302

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00302

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000590

Gnomad OTH AF: 0.00480

GnomAD4 exome AF: 0.000298 AC: 45 AN: 151220 Hom.: 0 AF XY: 0.000230 AC XY: 19 AN XY: 82524

Gnomad4 AFR exome AF: 0.0213

Gnomad4 AMR exome AF: 0.00129

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000639

GnomAD4 genome AF: 0.00865 AC: 1313 AN: 151806 Hom.: 21 Cov.: 31 AF XY: 0.00841 AC XY: 624 AN XY: 74192

Gnomad4 AFR AF: 0.0302

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000590

Gnomad4 OTH AF: 0.00475

Alfa AF: 0.00133 Hom.: 0

Bravo AF: 0.00943

Asia WGS AF: 0.00202 AC: 7 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 08, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	1.3
Dann	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs115259738; hg19: chr12-57943708;