NM_018131.5:c.204T>A

Variant names:

• chr10-93503133-T-A
• rs61865305
• NM_018131.5:c.204T>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_018131.5(CEP55):​c.204T>A​(p.Ala68Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0695 in 1,613,340 control chromosomes in the GnomAD database, including 4,452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (248 hom., cov: 33)
  • Exomes 𝑓: 0.072 (4204 hom.)
• Consequence: CEP55 NM_018131.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.721
• Publications: 7 publications found

Genes affected

CEP55 (HGNC:1161): (centrosomal protein 55) Enables identical protein binding activity. Involved in cranial skeletal system development; establishment of protein localization; and midbody abscission. Acts upstream of or within mitotic cytokinesis. Located in Flemming body; centriolar satellite; and plasma membrane. Implicated in multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly. [provided by Alliance of Genome Resources, Apr 2022]

CEP55 Gene-Disease associations (from GenCC):

• multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 10-93503133-T-A is Benign according to our data. Variant chr10-93503133-T-A is described in ClinVar as Benign. ClinVar VariationId is 1561146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.721 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018131.5. 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
	CEP55	NM_018131.5	MANE Select	c.204T>A	p.Ala68Ala	synonymous	Exon 3 of 9	NP_060601.4
	CEP55	NM_001127182.2		c.204T>A	p.Ala68Ala	synonymous	Exon 3 of 9	NP_001120654.2	Q53EZ4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP55	ENST00000371485.8	TSL:1 MANE Select	c.204T>A	p.Ala68Ala	synonymous	Exon 3 of 9	ENSP00000360540.3	Q53EZ4-1
	CEP55	ENST00000897343.1		c.204T>A	p.Ala68Ala	synonymous	Exon 3 of 9	ENSP00000567402.1
	CEP55	ENST00000912346.1		c.204T>A	p.Ala68Ala	synonymous	Exon 3 of 9	ENSP00000582405.1

Frequencies

GnomAD3 genomes AF: 0.0497 AC: 7565 AN: 152142 Hom.: 249 Cov.: 33

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.0455

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0184

Gnomad FIN AF: 0.0859

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0758

Gnomad OTH AF: 0.0435

GnomAD2 exomes AF: 0.0529 AC: 13255 AN: 250668 AF XY: 0.0528

Gnomad AFR exome AF: 0.0140

Gnomad AMR exome AF: 0.0280

Gnomad ASJ exome AF: 0.0433

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0902

Gnomad NFE exome AF: 0.0766

Gnomad OTH exome AF: 0.0596

GnomAD4 exome AF: 0.0715 AC: 104498 AN: 1461080 Hom.: 4204 Cov.: 31 AF XY: 0.0699 AC XY: 50782 AN XY: 726818

African (AFR) AF: 0.0111 AC: 373 AN: 33456

American (AMR) AF: 0.0281 AC: 1257 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.0428 AC: 1118 AN: 26100

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39692

South Asian (SAS) AF: 0.0211 AC: 1819 AN: 86106

European-Finnish (FIN) AF: 0.0867 AC: 4624 AN: 53306

Middle Eastern (MID) AF: 0.0408 AC: 235 AN: 5766

European-Non Finnish (NFE) AF: 0.0821 AC: 91290 AN: 1111620

Other (OTH) AF: 0.0626 AC: 3778 AN: 60360

GnomAD4 genome AF: 0.0497 AC: 7562 AN: 152260 Hom.: 248 Cov.: 33 AF XY: 0.0492 AC XY: 3664 AN XY: 74444

African (AFR) AF: 0.0146 AC: 605 AN: 41560

American (AMR) AF: 0.0346 AC: 529 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0455 AC: 158 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.0180 AC: 87 AN: 4828

European-Finnish (FIN) AF: 0.0859 AC: 910 AN: 10588

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0758 AC: 5157 AN: 68008

Other (OTH) AF: 0.0430 AC: 91 AN: 2116

Alfa AF: 0.0650 Hom.: 118

Bravo AF: 0.0453

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.0718

EpiControl AF: 0.0711

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	-0.45
CADD	Benign	8.6
DANN	Benign	0.82
PhyloP100		0.72
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs61865305; hg19: chr10-95262890;