rs369620316

Variant names:

• chr17-5023901-C-A
• rs369620316
• NM_006612.6:c.3062C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-5023901-C-A
• chr17-5023901-C-G
• chr17-5023901-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS1

The NM_006612.6(KIF1C):​c.3062C>A​(p.Pro1021Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000387 in 1,551,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1021L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: KIF1C NM_006612.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20247185).
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.00000357 (5/1399636) while in subpopulation EAS AF = 0.000103 (4/38916). AF 95% confidence interval is 0.000035. There are 0 homozygotes in GnomAdExome4. There are 3 alleles in the male GnomAdExome4 subpopulation. Median coverage is 35. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1C	NM_006612.6	c.3062C>A	p.Pro1021Gln	missense_variant	Exon 23 of 23	ENST00000320785.10	NP_006603.2
KIF1C	XM_005256424.3	c.3062C>A	p.Pro1021Gln	missense_variant	Exon 24 of 24		XP_005256481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1C	ENST00000320785.10	c.3062C>A	p.Pro1021Gln	missense_variant	Exon 23 of 23	1	NM_006612.6	ENSP00000320821.5
KIF1C-AS1	ENST00000438266.2	n.172-2946G>T		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000357 AC: 5 AN: 1399636 Hom.: 0 Cov.: 35 AF XY: 0.00000435 AC XY: 3 AN XY: 690110

African (AFR) AF: 0.00 AC: 0 AN: 31396

American (AMR) AF: 0.00 AC: 0 AN: 35432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21786

East Asian (EAS) AF: 0.000103 AC: 4 AN: 38916

South Asian (SAS) AF: 0.00 AC: 0 AN: 77136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5450

European-Non Finnish (NFE) AF: 9.25e-7 AC: 1 AN: 1080742

Other (OTH) AF: 0.00 AC: 0 AN: 57524

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74348

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.018
Eigen_PC	Benign	0.018
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.4
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.20
Sift	Benign	0.22	T
Sift4G	Benign	0.23	T
Polyphen		0.99	D
Vest4		0.15
MutPred		0.16		Loss of glycosylation at P1021 (P = 0.0049);
MVP		0.67
MPC		0.94
ClinPred		0.68	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.048
gMVP		0.48
Mutation Taster		=97/3	polymorphism

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: rs369620316; hg19: chr17-4927196;