Genetic Variant NM_001394669.1:c.*226T>C (chr17-82101456-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001394669.1(CCDC57):c.*226T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 346,590 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: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

CCDC57
NM_001394669.1 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.94

Publications

21 publications found

Variant links:

Genes affected

CCDC57 (HGNC:27564): (coiled-coil domain containing 57) Involved in several processes, including G2/M transition of mitotic cell cycle; cilium assembly; and microtubule cytoskeleton organization. Located in centriolar satellite; centriole; and spindle microtubule. [provided by Alliance of Genome Resources, Apr 2022]

CCDC57 links:

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ACMG classification

Classification was made for transcript

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 (BayesDel_noAF=-1.0).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC57	NM_001394669.1 link	c.*226T>C		downstream_gene_variant		ENST00000694881.1	NP_001381598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC57	ENST00000694881.1 link	c.*226T>C		downstream_gene_variant			NM_001394669.1	ENSP00000511565.1		A0A590UJT6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000289

AC:

AN:

346590

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

180032

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

8326

American (AMR)

AF:

0.00

AC:

AN:

9190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11632

East Asian (EAS)

AF:

0.00

AC:

AN:

23596

South Asian (SAS)

AF:

0.00

AC:

AN:

27588

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26166

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1704

European-Non Finnish (NFE)

AF:

0.00000461

AC:

AN:

216926

Other (OTH)

AF:

0.00

AC:

AN:

21462

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.13

(source)

DANN

Benign

0.37

PhyloP100

-1.9

PromoterAI

-0.018

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over