rs78356534

Positions:

• chr17-5020556-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006612.6(KIF1C):​c.1815G>A​(p.Leu605=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00519 in 1,614,222 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0053 (35 hom.)
• Consequence: KIF1C NM_006612.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.748

Genes affected

KIF1C (HGNC:6317): (kinesin family member 1C) The protein encoded by this gene is a member of the kinesin-like protein family. The family members are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. Mutations in this gene are a cause of spastic ataxia 2, autosomal recessive. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 17-5020556-G-A is Benign according to our data. Variant chr17-5020556-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 385064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.748 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00392 (597/152366) while in subpopulation NFE AF= 0.00594 (404/68030). AF 95% confidence interval is 0.00546. There are 2 homozygotes in gnomad4. There are 269 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF1C	NM_006612.6	c.1815G>A	p.Leu605=	synonymous_variant	20/23	ENST00000320785.10	NP_006603.2
KIF1C	XM_005256424.3	c.1815G>A	p.Leu605=	synonymous_variant	21/24		XP_005256481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF1C	ENST00000320785.10	c.1815G>A	p.Leu605=	synonymous_variant	20/23	1	NM_006612.6	ENSP00000320821	P1
KIF1C	ENST00000573815.1	n.357G>A		non_coding_transcript_exon_variant	4/6	5

Frequencies

GnomAD3 genomes AF: 0.00392 AC: 597 AN: 152248 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00594

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00445 AC: 1119 AN: 251238 Hom.: 8 AF XY: 0.00457 AC XY: 621 AN XY: 135854

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00243

Gnomad ASJ exome AF: 0.0200

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00134

Gnomad FIN exome AF: 0.000924

Gnomad NFE exome AF: 0.00626

Gnomad OTH exome AF: 0.00718

GnomAD4 exome AF: 0.00532 AC: 7778 AN: 1461856 Hom.: 35 Cov.: 33 AF XY: 0.00522 AC XY: 3798 AN XY: 727234

Gnomad4 AFR exome AF: 0.00116

Gnomad4 AMR exome AF: 0.00257

Gnomad4 ASJ exome AF: 0.0216

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00165

Gnomad4 FIN exome AF: 0.000899

Gnomad4 NFE exome AF: 0.00579

Gnomad4 OTH exome AF: 0.00611

GnomAD4 genome AF: 0.00392 AC: 597 AN: 152366 Hom.: 2 Cov.: 32 AF XY: 0.00361 AC XY: 269 AN XY: 74506

Gnomad4 AFR AF: 0.00106

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00594

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00640 Hom.: 0

Bravo AF: 0.00430

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00752

EpiControl AF: 0.00705

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2024	KIF1C: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 04, 2021	- -

Spastic ataxia 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Hereditary spastic paraplegia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Nov 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.3
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs78356534; hg19: chr17-4923851;