chr3-44775403-C-T

Variant names:

• chr3-44775403-C-T
• rs375356443
• NM_020242.3:c.212C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_020242.3(KIF15):​c.212C>T​(p.Thr71Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,612,838 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: KIF15 NM_020242.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.57
• Publications: 0 publications found

Genes affected

KIF15 (HGNC:17273): (kinesin family member 15) Predicted to enable microtubule binding activity and microtubule motor activity. Predicted to be involved in microtubule-based movement. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

KIF15 Gene-Disease associations (from GenCC):

• braddock-carey syndrome 2

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 3-44775403-C-T is Benign according to our data. Variant chr3-44775403-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3114477.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020242.3. 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
	KIF15	NM_020242.3	MANE Select	c.212C>T	p.Thr71Met	missense	Exon 3 of 35	NP_064627.1	Q9NS87-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF15	ENST00000326047.9	TSL:1 MANE Select	c.212C>T	p.Thr71Met	missense	Exon 3 of 35	ENSP00000324020.4	Q9NS87-1
	KIF15	ENST00000438321.5	TSL:1	n.169C>T		non_coding_transcript_exon	Exon 2 of 34	ENSP00000406939.1	F8WC33
	KIF15	ENST00000917498.1		c.212C>T	p.Thr71Met	missense	Exon 3 of 36	ENSP00000587557.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151894 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 250406 AF XY: 0.0000369

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: 0.0000529

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000390 AC: 57 AN: 1460944 Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28 AN XY: 726802

African (AFR) AF: 0.00 AC: 0 AN: 33422

American (AMR) AF: 0.00 AC: 0 AN: 44450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86184

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000477 AC: 53 AN: 1111572

Other (OTH) AF: 0.0000331 AC: 2 AN: 60346

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151894 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74170

African (AFR) AF: 0.00 AC: 0 AN: 41356

American (AMR) AF: 0.00 AC: 0 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000579 Hom.: 0

Bravo AF: 0.0000151

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Benign	0.65
DEOGEN2	Uncertain	0.52	D
Eigen	Benign	-0.0088
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Uncertain	-0.041	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		2.6
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.99	D
Vest4		0.38
MVP		0.71
MPC		0.25
ClinPred		0.66	D
GERP RS		2.2
Varity_R		0.14
gMVP		0.36
Mutation Taster		=54/46	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: rs375356443; hg19: chr3-44816895;