NM_001244008.2:c.3901+947T>C

Variant names:

• chr2-240739111-A-G
• rs3772054
• NM_001244008.2:c.3901+947T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001244008.2(KIF1A):​c.3901+947T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,112 control chromosomes in the GnomAD database, including 9,127 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (9127 hom., cov: 33)
• Consequence: KIF1A NM_001244008.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 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.3901+947T>C		intron	N/A	NP_001230937.1	Q12756-3
	KIF1A	NM_001379631.1		c.3976+947T>C		intron	N/A	NP_001366560.1
	KIF1A	NM_001379642.1		c.3874+947T>C		intron	N/A	NP_001366571.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1A	ENST00000498729.9	TSL:5 MANE Select	c.3901+947T>C		intron	N/A	ENSP00000438388.1	Q12756-3
	KIF1A	ENST00000492812.6	TSL:1	n.1063+947T>C		intron	N/A
	KIF1A	ENST00000675932.2		c.3901+947T>C		intron	N/A	ENSP00000502786.2	A0A6Q8PHQ5

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51920 AN: 151994 Hom.: 9104 Cov.: 33

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.353

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.342 AC: 51989 AN: 152112 Hom.: 9127 Cov.: 33 AF XY: 0.338 AC XY: 25130 AN XY: 74362

African (AFR) AF: 0.425 AC: 17615 AN: 41472

American (AMR) AF: 0.328 AC: 5022 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1270 AN: 3472

East Asian (EAS) AF: 0.307 AC: 1586 AN: 5170

South Asian (SAS) AF: 0.206 AC: 994 AN: 4824

European-Finnish (FIN) AF: 0.299 AC: 3170 AN: 10586

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21234 AN: 67984

Other (OTH) AF: 0.350 AC: 737 AN: 2108

Alfa AF: 0.327 Hom.: 25795

Bravo AF: 0.347

Asia WGS AF: 0.239 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.49
PhyloP100		-1.1
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: rs3772054; hg19: chr2-241678528; COSMIC: COSV57500193; COSMIC: COSV57500193;