chr4-56017651-A-T

Position:

• chr4-56017651-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025009.5(CEP135):​c.2806A>T​(p.Ile936Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000695 in 1,438,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CEP135 NM_025009.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.66

Genes affected

CEP135 (HGNC:29086): (centrosomal protein 135) This gene encodes a centrosomal protein, which acts as a scaffolding protein during early centriole biogenesis, and is also required for centriole-centriole cohesion during interphase. Mutations in this gene are associated with autosomal recessive primary microcephaly-8. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06211084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP135	NM_025009.5	c.2806A>T	p.Ile936Leu	missense_variant	22/26	ENST00000257287.5	NP_079285.2
CEP135	XM_006714055.4	c.2773A>T	p.Ile925Leu	missense_variant	22/26		XP_006714118.1
CEP135	XM_005265788.5	c.1735A>T	p.Ile579Leu	missense_variant	15/19		XP_005265845.1
CEP135	XM_011534412.2	c.1276A>T	p.Ile426Leu	missense_variant	12/16		XP_011532714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP135	ENST00000257287.5	c.2806A>T	p.Ile936Leu	missense_variant	22/26	1	NM_025009.5	ENSP00000257287	P1
CEP135	ENST00000506202.1	n.2756A>T		non_coding_transcript_exon_variant	15/19	1
CEP135	ENST00000706801.1	n.871A>T		non_coding_transcript_exon_variant	6/10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1438898 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 714068

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: 9.07e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.55
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	0.97	N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.056
Sift	Benign	1.0	T
Sift4G	Benign	0.56	T
Polyphen		0.0020	B
Vest4		0.29
MutPred		0.21		Loss of catalytic residue at I936 (P = 0.3464);
MVP		0.23
MPC		0.058
ClinPred		0.18	T
GERP RS		1.5
Varity_R		0.050
gMVP		0.092

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr4-56883817;