rs6667775

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-200553141-G-A
• chr1-200553141-G-C
• chr1-200553141-G-T

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.*247C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 237,336 control chromosomes in the GnomAD database, including 30,648 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (19626 hom., cov: 30)
  • Exomes 𝑓: 0.50 (11022 hom.)
• Consequence: KIF14 NM_014875.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 1-200553141-G-A is Benign according to our data. Variant chr1-200553141-G-A is described in ClinVar as Benign. ClinVar VariationId is 1283604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 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.*247C>T		3_prime_UTR	Exon 30 of 30	NP_055690.1	Q15058
	KIF14	NM_001305792.1		c.*247C>T		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>T		3_prime_UTR	Exon 30 of 30	ENSP00000356319.4	Q15058
	KIF14	ENST00000614960.4	TSL:1	c.*247C>T		3_prime_UTR	Exon 29 of 29	ENSP00000483069.1	Q15058
	KIF14	ENST00000928797.1		c.*247C>T		3_prime_UTR	Exon 31 of 31	ENSP00000598856.1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76772 AN: 151560 Hom.: 19632 Cov.: 30

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.540

GnomAD4 exome AF: 0.500 AC: 42847 AN: 85660 Hom.: 11022 Cov.: 3 AF XY: 0.504 AC XY: 22389 AN XY: 44444

African (AFR) AF: 0.477 AC: 1317 AN: 2760

American (AMR) AF: 0.494 AC: 1448 AN: 2932

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 1814 AN: 3116

East Asian (EAS) AF: 0.627 AC: 3956 AN: 6310

South Asian (SAS) AF: 0.598 AC: 1830 AN: 3060

European-Finnish (FIN) AF: 0.406 AC: 1818 AN: 4476

Middle Eastern (MID) AF: 0.570 AC: 228 AN: 400

European-Non Finnish (NFE) AF: 0.485 AC: 27771 AN: 57258

Other (OTH) AF: 0.498 AC: 2665 AN: 5348

GnomAD4 genome AF: 0.506 AC: 76804 AN: 151676 Hom.: 19626 Cov.: 30 AF XY: 0.506 AC XY: 37521 AN XY: 74084

African (AFR) AF: 0.489 AC: 20202 AN: 41338

American (AMR) AF: 0.518 AC: 7891 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2130 AN: 3468

East Asian (EAS) AF: 0.626 AC: 3211 AN: 5126

South Asian (SAS) AF: 0.611 AC: 2939 AN: 4810

European-Finnish (FIN) AF: 0.435 AC: 4568 AN: 10490

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.501 AC: 34041 AN: 67906

Other (OTH) AF: 0.539 AC: 1134 AN: 2102

Alfa AF: 0.468 Hom.: 2036

Bravo AF: 0.510

Asia WGS AF: 0.576 AC: 2001 AN: 3478

ClinVar

ClinVar submissions as Germline

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	0.047
DANN	Benign	0.62
PhyloP100		-1.8
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: rs6667775; hg19: chr1-200522269; COSMIC: COSV66260624;