rs776124283

Variant names:

• chr8-144466959-C-G
• rs776124283
• NM_001369769.2:c.179C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-144466959-C-G
• chr8-144466959-C-T

Variant summary

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

The NM_001369769.2(KIFC2):​c.179C>G​(p.Ala60Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,591,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A60V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 36)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KIFC2 NM_001369769.2 missense, splice_region
• Scores: Splicing: ADA: 0.00005387
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56
• Publications: 1 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: 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 (MetaRNN=0.05954075).

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.179C>G	p.Ala60Gly	missense splice_region	Exon 3 of 18	NP_001356698.1	A0A2R8YEU8
	KIFC2	NM_145754.5		c.179C>G	p.Ala60Gly	missense splice_region	Exon 3 of 17	NP_665697.1	Q96AC6-1
	TMEM276	NM_001408062.1		c.-202G>C		5_prime_UTR	Exon 1 of 3	NP_001394991.1	P0DTL5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIFC2	ENST00000645548.2	MANE Select	c.179C>G	p.Ala60Gly	missense splice_region	Exon 3 of 18	ENSP00000494595.1	A0A2R8YEU8
	KIFC2	ENST00000301332.3	TSL:1	c.179C>G	p.Ala60Gly	missense splice_region	Exon 3 of 17	ENSP00000301332.2	Q96AC6-1
	KIFC2	ENST00000880943.1		c.179C>G	p.Ala60Gly	missense splice_region	Exon 3 of 19	ENSP00000551002.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152198 Hom.: 0 Cov.: 36

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439764 Hom.: 0 Cov.: 72 AF XY: 0.00000140 AC XY: 1 AN XY: 716010

African (AFR) AF: 0.0000302 AC: 1 AN: 33150

American (AMR) AF: 0.00 AC: 0 AN: 43866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25710

East Asian (EAS) AF: 0.00 AC: 0 AN: 39312

South Asian (SAS) AF: 0.00 AC: 0 AN: 85054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5562

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107940

Other (OTH) AF: 0.00 AC: 0 AN: 59746

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152198 Hom.: 0 Cov.: 36 AF XY: 0.0000134 AC XY: 1 AN XY: 74358

African (AFR) AF: 0.0000241 AC: 1 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.76
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N
PhyloP100		2.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.098
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.043		Loss of stability (P = 0.0662)
MVP		0.33
ClinPred		0.048	T
GERP RS		0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.12
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000054
dbscSNV1_RF	Benign	0.066
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: rs776124283; hg19: chr8-145692342;