rs372031774

Positions:

• chr17-5023790-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006612.6(KIF1C):​c.2951A>C​(p.Asn984Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF1C NM_006612.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.17

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21673372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF1C	NM_006612.6	c.2951A>C	p.Asn984Thr	missense_variant	23/23	ENST00000320785.10	NP_006603.2
KIF1C	XM_005256424.3	c.2951A>C	p.Asn984Thr	missense_variant	24/24		XP_005256481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF1C	ENST00000320785.10	c.2951A>C	p.Asn984Thr	missense_variant	23/23	1	NM_006612.6	ENSP00000320821	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1366766 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 670244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000120 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spastic ataxia 2 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 25, 2018

This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with threonine at codon 984 of the KIF1C protein (p.Asn984Thr). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and threonine. This variant has not been reported in the literature in individuals with KIF1C-related disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.068
Eigen_PC	Benign	0.020
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.90	D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.41	N
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.58	P
Vest4		0.35
MVP		0.65
MPC		0.34
ClinPred		0.54	D
GERP RS		3.9
Varity_R		0.15
gMVP		0.58

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: rs372031774; hg19: chr17-4927085;