rs372031774

Variant names:

• chr17-5023790-A-C
• rs372031774
• NM_006612.6:c.2951A>C

Variant summary

Our verdict is Uncertain significance. The variant received 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N984K) has been classified 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
• Publications: 0 publications found

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]

KIF1C-AS1 (HGNC:40324): (KIF1C antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006612.6. 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
	KIF1C	NM_006612.6	MANE Select	c.2951A>C	p.Asn984Thr	missense	Exon 23 of 23	NP_006603.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1C	ENST00000320785.10	TSL:1 MANE Select	c.2951A>C	p.Asn984Thr	missense	Exon 23 of 23	ENSP00000320821.5	O43896
	KIF1C	ENST00000948910.1		c.2981A>C	p.Asn994Thr	missense	Exon 23 of 23	ENSP00000618969.1
	KIF1C	ENST00000948913.1		c.2981A>C	p.Asn994Thr	missense	Exon 22 of 22	ENSP00000618972.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 169374 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

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

African (AFR) AF: 0.00 AC: 0 AN: 30140

American (AMR) AF: 0.00 AC: 0 AN: 28918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19884

East Asian (EAS) AF: 0.00 AC: 0 AN: 38782

South Asian (SAS) AF: 0.00 AC: 0 AN: 70598

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5298

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1067686

Other (OTH) AF: 0.00 AC: 0 AN: 56134

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000120 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Spastic ataxia 2 (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		5.2
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

Other links and lift over

dbSNP: rs372031774; hg19: chr17-4927085;