NM_020242.3:c.632C>T

Variant names:

• chr3-44786567-C-T
• rs34862960
• NM_020242.3:c.632C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_020242.3(KIF15):​c.632C>T​(p.Ala211Val) variant causes a missense change. The variant allele was found at a frequency of 0.0032 in 1,609,804 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (13 hom.)
• Consequence: KIF15 NM_020242.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 6.17
• Publications: 7 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012339711).
• BP6: Variant 3-44786567-C-T is Benign according to our data. Variant chr3-44786567-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 717832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 Unknown gene

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.632C>T	p.Ala211Val	missense	Exon 7 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.632C>T	p.Ala211Val	missense	Exon 7 of 35	ENSP00000324020.4	Q9NS87-1
	KIF15	ENST00000438321.5	TSL:1	n.*337C>T		non_coding_transcript_exon	Exon 6 of 34	ENSP00000406939.1	F8WC33
	KIF15	ENST00000438321.5	TSL:1	n.*337C>T		3_prime_UTR	Exon 6 of 34	ENSP00000406939.1	F8WC33

Frequencies

GnomAD3 genomes AF: 0.00240 AC: 365 AN: 152138 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00370

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00323 AC: 810 AN: 250480 AF XY: 0.00347

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00128

Gnomad ASJ exome AF: 0.00229

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00208

Gnomad NFE exome AF: 0.00463

Gnomad OTH exome AF: 0.00377

GnomAD4 exome AF: 0.00328 AC: 4781 AN: 1457548 Hom.: 13 Cov.: 31 AF XY: 0.00340 AC XY: 2461 AN XY: 724656

African (AFR) AF: 0.000329 AC: 11 AN: 33426

American (AMR) AF: 0.00182 AC: 81 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.00239 AC: 62 AN: 25990

East Asian (EAS) AF: 0.00 AC: 0 AN: 39612

South Asian (SAS) AF: 0.00426 AC: 366 AN: 85832

European-Finnish (FIN) AF: 0.00193 AC: 103 AN: 53284

Middle Eastern (MID) AF: 0.00679 AC: 39 AN: 5744

European-Non Finnish (NFE) AF: 0.00354 AC: 3927 AN: 1108902

Other (OTH) AF: 0.00319 AC: 192 AN: 60180

GnomAD4 genome AF: 0.00241 AC: 367 AN: 152256 Hom.: 3 Cov.: 32 AF XY: 0.00251 AC XY: 187 AN XY: 74468

African (AFR) AF: 0.000433 AC: 18 AN: 41544

American (AMR) AF: 0.00209 AC: 32 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00436 AC: 21 AN: 4822

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10612

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.00371 AC: 252 AN: 68016

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00346 Hom.: 4

Bravo AF: 0.00221

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00384 AC: 33

ExAC AF: 0.00359 AC: 436

Asia WGS AF: 0.00318 AC: 13 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.091	T
Eigen	Benign	-0.026
Eigen_PC	Benign	0.14
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.045	N
PhyloP100		6.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.20
Sift	Benign	0.14	T
Sift4G	Uncertain	0.0080	D
Polyphen		0.50	P
Vest4		0.46
MVP		0.68
MPC		0.23
ClinPred		0.026	T
GERP RS		5.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.25
gMVP		0.48
Mutation Taster		=82/18	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: rs34862960; hg19: chr3-44828059; COSMIC: COSV58160880;