8-144466474-G-C

Variant names:

• chr8-144466474-G-C
• NM_001369769.2:c.55G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001408061.1(TMEM276):​c.-386C>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00001 in 1,195,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: TMEM276 NM_001408061.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.62

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4103455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFC2	NM_001369769.2	c.55G>C	p.Asp19His	missense_variant	Exon 1 of 18	ENST00000645548.2	NP_001356698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIFC2	ENST00000645548.2	c.55G>C	p.Asp19His	missense_variant	Exon 1 of 18		NM_001369769.2	ENSP00000494595.1
KIFC2	ENST00000301332.3	c.55G>C	p.Asp19His	missense_variant	Exon 1 of 17	1		ENSP00000301332.2
KIFC2	ENST00000642354.1	c.55G>C	p.Asp19His	missense_variant	Exon 1 of 18			ENSP00000496539.1
KIFC2	ENST00000643461.1	n.432G>C		non_coding_transcript_exon_variant	Exon 1 of 17

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000100 AC: 12 AN: 1195756 Hom.: 0 Cov.: 29 AF XY: 0.0000136 AC XY: 8 AN XY: 589652

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000113

Gnomad4 OTH exome AF: 0.0000218

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0089	.;.;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.70	T;T;T
M_CAP	Pathogenic	0.89	D
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	1.7	.;.;L
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.6	.;.;N
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	.;.;D
Sift4G	Pathogenic	0.0	.;.;D
Polyphen		1.0	.;.;D
Vest4		0.35
MutPred		0.34		Gain of MoRF binding (P = 0.0578);Gain of MoRF binding (P = 0.0578);Gain of MoRF binding (P = 0.0578);
MVP		0.85
ClinPred		0.93	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-145691857;