rs3732341

Variant names:

• chr2-240716127-G-A
• rs3732341
• NM_001244008.2:c.*1237C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-240716127-G-A
• chr2-240716127-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001244008.2(KIF1A):​c.*1237C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,770 control chromosomes in the GnomAD database, including 12,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (12148 hom., cov: 30)
  • Exomes 𝑓: 0.43 (18 hom.)
• Consequence: KIF1A NM_001244008.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00200
• Publications: 8 publications found

Genes affected

KIF1A (HGNC:888): (kinesin family member 1A) The protein encoded by this gene is a member of the kinesin family and functions as an anterograde motor protein that transports membranous organelles along axonal microtubules. Mutations at this locus have been associated with spastic paraplegia-30 and hereditary sensory neuropathy IIC. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Apr 2012]

KIF1A Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 9

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neuropathy, hereditary sensory, type 2C

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hereditary spastic paraplegia 30

  Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• PEHO syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary sensory and autonomic neuropathy type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-240716127-G-A is Benign according to our data. Variant chr2-240716127-G-A is described in ClinVar as Benign. ClinVar VariationId is 335240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244008.2. 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
	KIF1A	NM_001244008.2	MANE Select	c.*1237C>T		3_prime_UTR	Exon 49 of 49	NP_001230937.1	Q12756-3
	KIF1A	NM_001379631.1		c.*1237C>T		3_prime_UTR	Exon 49 of 49	NP_001366560.1
	KIF1A	NM_001379642.1		c.*1237C>T		3_prime_UTR	Exon 49 of 49	NP_001366571.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1A	ENST00000498729.9	TSL:5 MANE Select	c.*1237C>T		3_prime_UTR	Exon 49 of 49	ENSP00000438388.1	Q12756-3
	KIF1A	ENST00000460788.5	TSL:1	n.3170C>T		non_coding_transcript_exon	Exon 9 of 9
	KIF1A	ENST00000492812.6	TSL:1	n.5196C>T		non_coding_transcript_exon	Exon 16 of 16

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56029 AN: 151474 Hom.: 12144 Cov.: 30

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.420

GnomAD4 exome AF: 0.426 AC: 75 AN: 176 Hom.: 18 Cov.: 0 AF XY: 0.464 AC XY: 52 AN XY: 112

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.395 AC: 34 AN: 86

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.625 AC: 5 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.516 AC: 33 AN: 64

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.370 AC: 56045 AN: 151594 Hom.: 12148 Cov.: 30 AF XY: 0.368 AC XY: 27241 AN XY: 74054

African (AFR) AF: 0.160 AC: 6603 AN: 41336

American (AMR) AF: 0.406 AC: 6186 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1925 AN: 3472

East Asian (EAS) AF: 0.199 AC: 1018 AN: 5122

South Asian (SAS) AF: 0.272 AC: 1298 AN: 4776

European-Finnish (FIN) AF: 0.455 AC: 4765 AN: 10484

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32766 AN: 67838

Other (OTH) AF: 0.417 AC: 880 AN: 2110

Alfa AF: 0.439 Hom.: 14992

Bravo AF: 0.359

Asia WGS AF: 0.232 AC: 805 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary spastic paraplegia 30 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.56
PhyloP100		-0.0020
Mutation Taster		=100/0	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: rs3732341; hg19: chr2-241655544;