rs1678542

Variant names:

• chr12-57574932-C-G
• rs1678542
• NM_004984.4:c.1717-152C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-57574932-C-G
• chr12-57574932-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004984.4(KIF5A):​c.1717-152C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 707,348 control chromosomes in the GnomAD database, including 71,580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (14219 hom., cov: 30)
  • Exomes 𝑓: 0.44 (57361 hom.)
• Consequence: KIF5A NM_004984.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.211
• Publications: 77 publications found

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 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis, susceptibility to, 25

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Illumina
• inherited neurodegenerative disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• myoclonus, intractable, neonatal

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
• hereditary spastic paraplegia 10

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
• autosomal dominant Charcot-Marie-Tooth disease type 2 due to KIF5A mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 12-57574932-C-G is Benign according to our data. Variant chr12-57574932-C-G is described in ClinVar as Benign. ClinVar VariationId is 682870.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004984.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF5A	NM_004984.4	MANE Select	c.1717-152C>G		intron	N/A	NP_004975.2
	KIF5A	NM_001354705.2		c.1450-152C>G		intron	N/A	NP_001341634.1	J3KNA1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF5A	ENST00000455537.7	TSL:1 MANE Select	c.1717-152C>G		intron	N/A	ENSP00000408979.2	Q12840
	KIF5A	ENST00000674619.1		c.1717-152C>G		intron	N/A	ENSP00000502270.1	A0A6Q8PGJ3
	KIF5A	ENST00000938849.1		c.1717-152C>G		intron	N/A	ENSP00000608908.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64352 AN: 151842 Hom.: 14181 Cov.: 30

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.395

GnomAD4 exome AF: 0.436 AC: 241959 AN: 555388 Hom.: 57361 AF XY: 0.442 AC XY: 131285 AN XY: 297040

African (AFR) AF: 0.424 AC: 6547 AN: 15448

American (AMR) AF: 0.501 AC: 15905 AN: 31778

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 6853 AN: 18406

East Asian (EAS) AF: 0.790 AC: 25132 AN: 31802

South Asian (SAS) AF: 0.587 AC: 34126 AN: 58180

European-Finnish (FIN) AF: 0.511 AC: 19453 AN: 38100

Middle Eastern (MID) AF: 0.335 AC: 818 AN: 2444

European-Non Finnish (NFE) AF: 0.366 AC: 120307 AN: 329044

Other (OTH) AF: 0.425 AC: 12818 AN: 30186

GnomAD4 genome AF: 0.424 AC: 64444 AN: 151960 Hom.: 14219 Cov.: 30 AF XY: 0.436 AC XY: 32389 AN XY: 74264

African (AFR) AF: 0.421 AC: 17428 AN: 41420

American (AMR) AF: 0.439 AC: 6709 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1274 AN: 3464

East Asian (EAS) AF: 0.771 AC: 3984 AN: 5166

South Asian (SAS) AF: 0.606 AC: 2914 AN: 4812

European-Finnish (FIN) AF: 0.537 AC: 5658 AN: 10546

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.369 AC: 25082 AN: 67952

Other (OTH) AF: 0.401 AC: 846 AN: 2110

Alfa AF: 0.395 Hom.: 6953

Bravo AF: 0.417

Asia WGS AF: 0.657 AC: 2284 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.6
DANN	Benign	0.26
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1678542; hg19: chr12-57968715;