1-200553141-G-C

Variant names:

• chr1-200553141-G-C
• rs6667775
• NM_014875.3:c.*247C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014875.3(KIF14):​c.*247C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF14 NM_014875.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 5 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• microcephaly 20, primary, autosomal recessive

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).

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.*247C>G		3_prime_UTR	Exon 30 of 30	NP_055690.1	Q15058
	KIF14	NM_001305792.1		c.*247C>G		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.*247C>G		3_prime_UTR	Exon 30 of 30	ENSP00000356319.4	Q15058
	KIF14	ENST00000614960.4	TSL:1	c.*247C>G		3_prime_UTR	Exon 29 of 29	ENSP00000483069.1	Q15058
	KIF14	ENST00000928797.1		c.*247C>G		3_prime_UTR	Exon 31 of 31	ENSP00000598856.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 86104 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 44674

African (AFR) AF: 0.00 AC: 0 AN: 2776

American (AMR) AF: 0.00 AC: 0 AN: 2950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3122

East Asian (EAS) AF: 0.00 AC: 0 AN: 6346

South Asian (SAS) AF: 0.00 AC: 0 AN: 3074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 400

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 57560

Other (OTH) AF: 0.00 AC: 0 AN: 5382

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 2036

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.026
DANN	Benign	0.34
PhyloP100		-1.8

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: rs6667775; hg19: chr1-200522269;