2-148875587-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004522.3(KIF5C):c.-31T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 30)
  • Exomes 𝑓: 0.030 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF5C NM_004522.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.269

Genes affected

KIF5C (HGNC:6325): (kinesin family member 5C) The protein encoded by this gene is a kinesin heavy chain subunit involved in the transport of cargo within the central nervous system. The encoded protein, which acts as a tetramer by associating with another heavy chain and two light chains, interacts with protein kinase CK2. Mutations in this gene have been associated with complex cortical dysplasia with other brain malformations-2. Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Jul 2015]

KIF5C-AS1 (HGNC:40325): (KIF5C antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 2-148875587-T-C is Benign according to our data. Variant chr2-148875587-T-C is described in ClinVar as [Benign]. Clinvar id is 1277980.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome at 96 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF5C	NM_004522.3	c.-31T>C		5_prime_UTR_variant	1/26	ENST00000435030.6
KIF5C-AS1	XR_001739733.2	n.7731A>G		non_coding_transcript_exon_variant	4/4
KIF5C	XM_017004062.2	c.-31T>C		5_prime_UTR_variant	1/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF5C	ENST00000435030.6	c.-31T>C		5_prime_UTR_variant	1/26	1	NM_004522.3	P4
KIF5C-AS1	ENST00000601658.5	n.676+1639A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 4 AN: 101672 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000381

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000446

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000207

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00115 AC: 96 AN: 83652 Hom.: 0 AF XY: 0.00107 AC XY: 51 AN XY: 47578

Gnomad AFR exome AF: 0.000279

Gnomad AMR exome AF: 0.00313

Gnomad ASJ exome AF: 0.000824

Gnomad EAS exome AF: 0.00217

Gnomad SAS exome AF: 0.00102

Gnomad FIN exome AF: 0.00175

Gnomad NFE exome AF: 0.000549

Gnomad OTH exome AF: 0.00202

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0297 AC: 7446 AN: 250332 Hom.: 0 Cov.: 0 AF XY: 0.0266 AC XY: 3603 AN XY: 135276

Gnomad4 AFR exome AF: 0.0283

Gnomad4 AMR exome AF: 0.0212

Gnomad4 ASJ exome AF: 0.0158

Gnomad4 EAS exome AF: 0.0151

Gnomad4 SAS exome AF: 0.00979

Gnomad4 FIN exome AF: 0.00546

Gnomad4 NFE exome AF: 0.0414

Gnomad4 OTH exome AF: 0.0265

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000393 AC: 4 AN: 101716 Hom.: 0 Cov.: 30 AF XY: 0.0000205 AC XY: 1 AN XY: 48794

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000381

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000446

Gnomad4 NFE AF: 0.0000207

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 17, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	15
Dann	Benign	0.90

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: rs1558866657; hg19: chr2-149633156;