chr1-200553223-A-T

Variant names:

• chr1-200553223-A-T
• rs10800708
• NM_014875.3:c.*165T>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.*165T>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 0.57 in 712,532 control chromosomes in the GnomAD database, including 117,908 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (22138 hom., cov: 33)
  • Exomes 𝑓: 0.58 (95770 hom.)
• Consequence: KIF14 NM_014875.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0260
• Publications: 8 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=-0.9).
• BP6: Variant 1-200553223-A-T is Benign according to our data. Variant chr1-200553223-A-T is described in ClinVar as Benign. ClinVar VariationId is 1286174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 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.*165T>A		3_prime_UTR	Exon 30 of 30	NP_055690.1	Q15058
	KIF14	NM_001305792.1		c.*165T>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.*165T>A		3_prime_UTR	Exon 30 of 30	ENSP00000356319.4	Q15058
	KIF14	ENST00000614960.4	TSL:1	c.*165T>A		3_prime_UTR	Exon 29 of 29	ENSP00000483069.1	Q15058
	KIF14	ENST00000928797.1		c.*165T>A		3_prime_UTR	Exon 31 of 31	ENSP00000598856.1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80579 AN: 151958 Hom.: 22136 Cov.: 33

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.592

GnomAD4 exome AF: 0.580 AC: 325264 AN: 560456 Hom.: 95770 Cov.: 8 AF XY: 0.583 AC XY: 167937 AN XY: 288138

African (AFR) AF: 0.385 AC: 5170 AN: 13430

American (AMR) AF: 0.512 AC: 9496 AN: 18560

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 8362 AN: 12648

East Asian (EAS) AF: 0.691 AC: 19772 AN: 28618

South Asian (SAS) AF: 0.639 AC: 20270 AN: 31700

European-Finnish (FIN) AF: 0.520 AC: 14367 AN: 27634

Middle Eastern (MID) AF: 0.607 AC: 1162 AN: 1914

European-Non Finnish (NFE) AF: 0.579 AC: 230527 AN: 398170

Other (OTH) AF: 0.581 AC: 16138 AN: 27782

GnomAD4 genome AF: 0.530 AC: 80614 AN: 152076 Hom.: 22138 Cov.: 33 AF XY: 0.532 AC XY: 39536 AN XY: 74326

African (AFR) AF: 0.387 AC: 16072 AN: 41492

American (AMR) AF: 0.555 AC: 8475 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2267 AN: 3472

East Asian (EAS) AF: 0.690 AC: 3570 AN: 5172

South Asian (SAS) AF: 0.641 AC: 3090 AN: 4824

European-Finnish (FIN) AF: 0.523 AC: 5528 AN: 10562

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39656 AN: 67972

Other (OTH) AF: 0.593 AC: 1251 AN: 2108

Alfa AF: 0.535 Hom.: 2753

Bravo AF: 0.524

Asia WGS AF: 0.659 AC: 2291 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	-0.90
CADD	Benign	1.8
DANN	Benign	0.75
PhyloP100		-0.026
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: rs10800708; hg19: chr1-200522351; COSMIC: COSV66261507;