6-33409703-ATC-ATCTC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002263.4(KIFC1):c.*15_*16dup variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 1,320,974 control chromosomes in the GnomAD database, including 2,522 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (255 hom., cov: 28)
  • Exomes 𝑓: 0.021 (2267 hom.)
• Consequence: KIFC1 NM_002263.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.491

Genes affected

KIFC1 (HGNC:6389): (kinesin family member C1) Predicted to enable microtubule binding activity and minus-end-directed microtubule motor activity. Involved in mitotic metaphase plate congression and mitotic spindle assembly. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 6-33409703-A-ATC is Benign according to our data. Variant chr6-33409703-A-ATC is described in ClinVar as [Benign]. Clinvar id is 403017.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIFC1	NM_002263.4	c.*15_*16dup		3_prime_UTR_variant	11/11	ENST00000428849.7
KIFC1	XM_011514585.2	c.*100_*101dup		3_prime_UTR_variant	12/12
KIFC1	XM_011514587.3	c.*15_*16dup		3_prime_UTR_variant	10/10
KIFC1	XM_017010837.2	c.*15_*16dup		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIFC1	ENST00000428849.7	c.*15_*16dup		3_prime_UTR_variant	11/11	1	NM_002263.4	P1

Frequencies

GnomAD3 genomes AF: 0.0610 AC: 5297 AN: 86778 Hom.: 255 Cov.: 28

Gnomad AFR AF: 0.0497

Gnomad AMI AF: 0.00147

Gnomad AMR AF: 0.0745

Gnomad ASJ AF: 0.0592

Gnomad EAS AF: 0.0792

Gnomad SAS AF: 0.0594

Gnomad FIN AF: 0.0968

Gnomad MID AF: 0.0455

Gnomad NFE AF: 0.0614

Gnomad OTH AF: 0.0593

GnomAD3 exomes AF: 0.0250 AC: 4808 AN: 192512 Hom.: 333 AF XY: 0.0252 AC XY: 2644 AN XY: 104726

Gnomad AFR exome AF: 0.0121

Gnomad AMR exome AF: 0.0356

Gnomad ASJ exome AF: 0.0157

Gnomad EAS exome AF: 0.0299

Gnomad SAS exome AF: 0.0240

Gnomad FIN exome AF: 0.0387

Gnomad NFE exome AF: 0.0223

Gnomad OTH exome AF: 0.0274

GnomAD4 exome AF: 0.0205 AC: 25339 AN: 1234106 Hom.: 2267 Cov.: 34 AF XY: 0.0211 AC XY: 13017 AN XY: 617934

Gnomad4 AFR exome AF: 0.0116

Gnomad4 AMR exome AF: 0.0344

Gnomad4 ASJ exome AF: 0.0202

Gnomad4 EAS exome AF: 0.0388

Gnomad4 SAS exome AF: 0.0230

Gnomad4 FIN exome AF: 0.0422

Gnomad4 NFE exome AF: 0.0184

Gnomad4 OTH exome AF: 0.0227

GnomAD4 genome AF: 0.0610 AC: 5301 AN: 86868 Hom.: 255 Cov.: 28 AF XY: 0.0623 AC XY: 2569 AN XY: 41238

Gnomad4 AFR AF: 0.0498

Gnomad4 AMR AF: 0.0743

Gnomad4 ASJ AF: 0.0592

Gnomad4 EAS AF: 0.0789

Gnomad4 SAS AF: 0.0590

Gnomad4 FIN AF: 0.0968

Gnomad4 NFE AF: 0.0614

Gnomad4 OTH AF: 0.0591

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs752059822; hg19: chr6-33377480;