rs147337582

Variant names:

• chr1-200553391-C-A
• rs147337582
• NM_014875.3:c.4944G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-200553391-C-A
• chr1-200553391-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_014875.3(KIF14):​c.4944G>T​(p.Val1648Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,600,254 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. V1648V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: KIF14 NM_014875.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.143
• Publications: 0 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 1-200553391-C-A is Benign according to our data. Variant chr1-200553391-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 739562.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.143 with no splicing effect.

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.4944G>T	p.Val1648Val	synonymous	Exon 30 of 30	NP_055690.1	Q15058
	KIF14	NM_001305792.1		c.3471G>T	p.Val1157Val	synonymous	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.4944G>T	p.Val1648Val	synonymous	Exon 30 of 30	ENSP00000356319.4	Q15058
	KIF14	ENST00000614960.4	TSL:1	c.4944G>T	p.Val1648Val	synonymous	Exon 29 of 29	ENSP00000483069.1	Q15058
	KIF14	ENST00000928797.1		c.5061G>T	p.Val1687Val	synonymous	Exon 31 of 31	ENSP00000598856.1

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000196 AC: 47 AN: 240164 AF XY: 0.000170

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.000311

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000472

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.000344

GnomAD4 exome AF: 0.000207 AC: 300 AN: 1448100 Hom.: 1 Cov.: 29 AF XY: 0.000183 AC XY: 132 AN XY: 719388

African (AFR) AF: 0.0000610 AC: 2 AN: 32796

American (AMR) AF: 0.000285 AC: 12 AN: 42078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25292

East Asian (EAS) AF: 0.00 AC: 0 AN: 39584

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83630

European-Finnish (FIN) AF: 0.0000377 AC: 2 AN: 53090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 0.000249 AC: 275 AN: 1106158

Other (OTH) AF: 0.000134 AC: 8 AN: 59798

GnomAD4 genome AF: 0.000191 AC: 29 AN: 152154 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74312

African (AFR) AF: 0.0000483 AC: 2 AN: 41434

American (AMR) AF: 0.000262 AC: 4 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68034

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000238

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	2.3
DANN	Benign	0.73
PhyloP100		-0.14
Mutation Taster		=99/1	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: rs147337582; hg19: chr1-200522519;