NM_014875.3:c.*231G>A

Variant names:

• chr1-200553157-C-T
• rs112727234
• NM_014875.3:c.*231G>A

Variant summary

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

The NM_014875.3(KIF14):​c.*231G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 286,084 control chromosomes in the GnomAD database, including 2,509 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1435 hom., cov: 32)
  • Exomes 𝑓: 0.12 (1074 hom.)
• Consequence: KIF14 NM_014875.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.75
• Publications: 3 publications found

Genes affected

KIF14 (HGNC:19181): (kinesin family member 14) This gene encodes a member of the kinesin-3 superfamily of microtubule motor proteins. These proteins are involved in numerous processes including vesicle transport, chromosome segregation, mitotic spindle formation, and cytokinesis. In human HeLa-S3 and 293T cells, this protein is localized to the cytoplasm during interphase, to the spindle poles and spindle microtubules during mitosis, and to the midbody during cytokinesis. An internal motor domain displays microtubule-dependent ATPase activity, consistent with its function as a microtubule motor protein. Knockdown of this gene results in failed cytokinesis with endoreplication, which results in multinucleated cells. This gene has been identified as a likely oncogene in breast, lung and ovarian cancers, as well as retinoblastomas and gliomas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2015]

KIF14 Gene-Disease associations (from GenCC):

• autosomal recessive primary microcephaly

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Illumina
• lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• microcephaly 20, primary, autosomal recessive

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 1-200553157-C-T is Benign according to our data. Variant chr1-200553157-C-T is described in ClinVar as Benign. ClinVar VariationId is 1265811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014875.3. 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
	KIF14	NM_014875.3	MANE Select	c.*231G>A		3_prime_UTR	Exon 30 of 30	NP_055690.1	Q15058
	KIF14	NM_001305792.1		c.*231G>A		3_prime_UTR	Exon 28 of 28	NP_001292721.1	Q15058

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF14	ENST00000367350.5	TSL:2 MANE Select	c.*231G>A		3_prime_UTR	Exon 30 of 30	ENSP00000356319.4	Q15058
	KIF14	ENST00000614960.4	TSL:1	c.*231G>A		3_prime_UTR	Exon 29 of 29	ENSP00000483069.1	Q15058
	KIF14	ENST00000928797.1		c.*231G>A		3_prime_UTR	Exon 31 of 31	ENSP00000598856.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19328 AN: 151772 Hom.: 1434 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.0919

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.115 AC: 15452 AN: 134194 Hom.: 1074 Cov.: 4 AF XY: 0.114 AC XY: 7960 AN XY: 69934

African (AFR) AF: 0.139 AC: 547 AN: 3944

American (AMR) AF: 0.0728 AC: 324 AN: 4448

Ashkenazi Jewish (ASJ) AF: 0.0669 AC: 311 AN: 4648

East Asian (EAS) AF: 0.000106 AC: 1 AN: 9408

South Asian (SAS) AF: 0.0201 AC: 109 AN: 5422

European-Finnish (FIN) AF: 0.188 AC: 1481 AN: 7882

Middle Eastern (MID) AF: 0.0519 AC: 32 AN: 616

European-Non Finnish (NFE) AF: 0.131 AC: 11732 AN: 89598

Other (OTH) AF: 0.111 AC: 915 AN: 8228

GnomAD4 genome AF: 0.127 AC: 19333 AN: 151890 Hom.: 1435 Cov.: 32 AF XY: 0.126 AC XY: 9354 AN XY: 74212

African (AFR) AF: 0.146 AC: 6053 AN: 41436

American (AMR) AF: 0.0919 AC: 1400 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.0643 AC: 223 AN: 3470

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5158

South Asian (SAS) AF: 0.0156 AC: 75 AN: 4820

European-Finnish (FIN) AF: 0.200 AC: 2101 AN: 10498

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9174 AN: 67960

Other (OTH) AF: 0.105 AC: 220 AN: 2102

Alfa AF: 0.0746 Hom.: 94

Bravo AF: 0.119

Asia WGS AF: 0.0180 AC: 64 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.70
DANN	Benign	0.46
PhyloP100		-3.7
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: rs112727234; hg19: chr1-200522285;