chr8-144466443-C-T

Variant names:

• chr8-144466443-C-T
• rs142310829
• NM_001369769.2:c.24C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001369769.2(KIFC2):​c.24C>T​(p.Leu8Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,363,372 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L8L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 30)
  • Exomes 𝑓: 0.0016 (29 hom.)
• Consequence: KIFC2 NM_001369769.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0820
• Publications: 0 publications found

Genes affected

KIFC2 (HGNC:29530): (kinesin family member C2) Predicted to enable microtubule binding activity and microtubule motor activity. Predicted to be involved in microtubule-based movement and mitotic spindle assembly. Predicted to be located in cytoplasm. Predicted to be part of kinesin complex. Predicted to be active in microtubule cytoskeleton and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TMEM276 (HGNC:56235): (transmembrane protein 276)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 8-144466443-C-T is Benign according to our data. Variant chr8-144466443-C-T is described in ClinVar as Benign. ClinVar VariationId is 782144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.082 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00278 (417/150082) while in subpopulation SAS AF = 0.0193 (93/4814). AF 95% confidence interval is 0.0161. There are 1 homozygotes in GnomAd4. There are 223 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 29 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369769.2. 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
	KIFC2	NM_001369769.2	MANE Select	c.24C>T	p.Leu8Leu	synonymous	Exon 1 of 18	NP_001356698.1	A0A2R8YEU8
	KIFC2	NM_145754.5		c.24C>T	p.Leu8Leu	synonymous	Exon 1 of 17	NP_665697.1	Q96AC6-1
	TMEM276	NM_001408061.1		c.-355G>A		5_prime_UTR	Exon 1 of 3	NP_001394990.1	P0DTL5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIFC2	ENST00000645548.2	MANE Select	c.24C>T	p.Leu8Leu	synonymous	Exon 1 of 18	ENSP00000494595.1	A0A2R8YEU8
	KIFC2	ENST00000301332.3	TSL:1	c.24C>T	p.Leu8Leu	synonymous	Exon 1 of 17	ENSP00000301332.2	Q96AC6-1
	KIFC2	ENST00000880943.1		c.24C>T	p.Leu8Leu	synonymous	Exon 1 of 19	ENSP00000551002.1

Frequencies

GnomAD3 genomes AF: 0.00272 AC: 408 AN: 149974 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00450

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00384

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.00216

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.000101

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.000670

Gnomad OTH AF: 0.00436

GnomAD2 exomes AF: 0.00350 AC: 488 AN: 139430 AF XY: 0.00434

Gnomad AFR exome AF: 0.00280

Gnomad AMR exome AF: 0.00144

Gnomad ASJ exome AF: 0.000146

Gnomad EAS exome AF: 0.000150

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000673

Gnomad OTH exome AF: 0.00336

GnomAD4 exome AF: 0.00159 AC: 1933 AN: 1213290 Hom.: 29 Cov.: 29 AF XY: 0.00190 AC XY: 1140 AN XY: 600682

African (AFR) AF: 0.00463 AC: 112 AN: 24212

American (AMR) AF: 0.00163 AC: 38 AN: 23350

Ashkenazi Jewish (ASJ) AF: 0.000110 AC: 2 AN: 18192

East Asian (EAS) AF: 0.00246 AC: 60 AN: 24394

South Asian (SAS) AF: 0.0190 AC: 1074 AN: 56552

European-Finnish (FIN) AF: 0.0000263 AC: 1 AN: 37964

Middle Eastern (MID) AF: 0.00812 AC: 38 AN: 4680

European-Non Finnish (NFE) AF: 0.000487 AC: 476 AN: 977722

Other (OTH) AF: 0.00286 AC: 132 AN: 46224

GnomAD4 genome AF: 0.00278 AC: 417 AN: 150082 Hom.: 1 Cov.: 30 AF XY: 0.00304 AC XY: 223 AN XY: 73310

African (AFR) AF: 0.00458 AC: 189 AN: 41240

American (AMR) AF: 0.00383 AC: 58 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.000290 AC: 1 AN: 3446

East Asian (EAS) AF: 0.00217 AC: 11 AN: 5080

South Asian (SAS) AF: 0.0193 AC: 93 AN: 4814

European-Finnish (FIN) AF: 0.000101 AC: 1 AN: 9916

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.000670 AC: 45 AN: 67162

Other (OTH) AF: 0.00671 AC: 14 AN: 2086

Alfa AF: 0.000156 Hom.: 0

Asia WGS AF: 0.0180 AC: 59 AN: 3172

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	-0.59
CADD	Benign	12
DANN	Benign	0.93
PhyloP100		-0.082
PromoterAI		0.14	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs142310829; hg19: chr8-145691826;