chr17-5022379-C-T

Variant names:

• chr17-5022379-C-T
• rs73345356
• NM_006612.6:c.2298C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The ENST00000320785.10(KIF1C):​c.2298C>T​(p.His766His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00785 in 1,581,366 control chromosomes in the GnomAD database, including 562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (286 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (276 hom.)
• Consequence: KIF1C ENST00000320785.10 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.196
• Publications: 1 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 17-5022379-C-T is Benign according to our data. Variant chr17-5022379-C-T is described in ClinVar as Benign. ClinVar VariationId is 387794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.196 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000320785.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1C	NM_006612.6	MANE Select	c.2298C>T	p.His766His	synonymous	Exon 22 of 23	NP_006603.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1C	ENST00000320785.10	TSL:1 MANE Select	c.2298C>T	p.His766His	synonymous	Exon 22 of 23	ENSP00000320821.5
	KIF1C-AS1	ENST00000438266.2	TSL:2	n.172-1424G>A		intron	N/A
	KIF1C	ENST00000573815.1	TSL:5	n.*114C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0342 AC: 5209 AN: 152256 Hom.: 285 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00187

Gnomad OTH AF: 0.0224

GnomAD2 exomes AF: 0.00920 AC: 1794 AN: 195036 AF XY: 0.00651

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.00845

Gnomad ASJ exome AF: 0.000446

Gnomad EAS exome AF: 0.0000695

Gnomad FIN exome AF: 0.0000552

Gnomad NFE exome AF: 0.00195

Gnomad OTH exome AF: 0.00662

GnomAD4 exome AF: 0.00504 AC: 7195 AN: 1428992 Hom.: 276 Cov.: 32 AF XY: 0.00453 AC XY: 3207 AN XY: 708168

African (AFR) AF: 0.120 AC: 3949 AN: 32774

American (AMR) AF: 0.00906 AC: 357 AN: 39390

Ashkenazi Jewish (ASJ) AF: 0.000707 AC: 18 AN: 25458

East Asian (EAS) AF: 0.0000263 AC: 1 AN: 37986

South Asian (SAS) AF: 0.000386 AC: 32 AN: 82850

European-Finnish (FIN) AF: 0.000274 AC: 14 AN: 51060

Middle Eastern (MID) AF: 0.00768 AC: 44 AN: 5732

European-Non Finnish (NFE) AF: 0.00202 AC: 2210 AN: 1094614

Other (OTH) AF: 0.00964 AC: 570 AN: 59128

GnomAD4 genome AF: 0.0343 AC: 5219 AN: 152374 Hom.: 286 Cov.: 32 AF XY: 0.0324 AC XY: 2414 AN XY: 74510

African (AFR) AF: 0.114 AC: 4739 AN: 41592

American (AMR) AF: 0.0192 AC: 294 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.000376 AC: 4 AN: 10628

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00187 AC: 127 AN: 68038

Other (OTH) AF: 0.0222 AC: 47 AN: 2116

Alfa AF: 0.0159 Hom.: 47

Bravo AF: 0.0395

Asia WGS AF: 0.00693 AC: 26 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary spastic paraplegia (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Spastic ataxia 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	2.0
DANN	Benign	0.84
PhyloP100		-0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=99/1	polymorphism (auto)

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: rs73345356; hg19: chr17-4925674;