2-148875574-G-C

Variant names:

• chr2-148875574-G-C
• rs557953832
• NM_004522.3:c.-44G>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004522.3(KIF5C):​c.-44G>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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000057 (0 hom., cov: 33)
  • Exomes 𝑓: 0.011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF5C NM_004522.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF5C	NM_004522.3	c.-44G>C		5_prime_UTR_variant	Exon 1 of 26	ENST00000435030.6	NP_004513.1
KIF5C	XM_017004062.2	c.-44G>C		5_prime_UTR_variant	Exon 1 of 26		XP_016859551.1
KIF5C-AS1	XR_001739733.2	n.7744C>G		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF5C	ENST00000435030	c.-44G>C		5_prime_UTR_variant	Exon 1 of 26	1	NM_004522.3	ENSP00000393379.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 8 AN: 140592 Hom.: 0 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.0000516

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000210

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000354

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00380 AC: 404 AN: 106178 Hom.: 0 AF XY: 0.00344 AC XY: 202 AN XY: 58648

Gnomad AFR exome AF: 0.00314

Gnomad AMR exome AF: 0.00948

Gnomad ASJ exome AF: 0.00417

Gnomad EAS exome AF: 0.00509

Gnomad SAS exome AF: 0.00217

Gnomad FIN exome AF: 0.00376

Gnomad NFE exome AF: 0.00222

Gnomad OTH exome AF: 0.00564

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0109 AC: 3798 AN: 349204 Hom.: 0 Cov.: 3 AF XY: 0.0112 AC XY: 2157 AN XY: 191782

Gnomad4 AFR exome AF: 0.0117

Gnomad4 AMR exome AF: 0.0236

Gnomad4 ASJ exome AF: 0.00846

Gnomad4 EAS exome AF: 0.00206

Gnomad4 SAS exome AF: 0.0146

Gnomad4 FIN exome AF: 0.00701

Gnomad4 NFE exome AF: 0.0101

Gnomad4 OTH exome AF: 0.0106

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000569 AC: 8 AN: 140690 Hom.: 0 Cov.: 33 AF XY: 0.0000439 AC XY: 3 AN XY: 68314

Gnomad4 AFR AF: 0.0000514

Gnomad4 AMR AF: 0.000210

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000354

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00485 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.88

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: rs557953832; hg19: chr2-149633143;