1-3756859-T-C

Position:

• chr1-3756859-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_152492.3(CCDC27):​c.680T>C​(p.Met227Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC27 NM_152492.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.111

Genes affected

CCDC27 (HGNC:26546): (coiled-coil domain containing 27)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046593726).
• BP6: Variant 1-3756859-T-C is Benign according to our data. Variant chr1-3756859-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2295719.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC27	NM_152492.3	c.680T>C	p.Met227Thr	missense_variant	4/12	ENST00000294600.7	NP_689705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC27	ENST00000294600.7	c.680T>C	p.Met227Thr	missense_variant	4/12	1	NM_152492.3	ENSP00000294600	P1
CCDC27	ENST00000636250.1	n.2355T>C		non_coding_transcript_exon_variant	6/6	5
CCDC27	ENST00000462521.2	c.*52T>C		3_prime_UTR_variant, NMD_transcript_variant	4/12	5		ENSP00000463275

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251154 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135808

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 17, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.053
DANN	Benign	0.22
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.14	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.015
Sift	Benign	0.31	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.28		Loss of stability (P = 0.0472);
MVP		0.16
MPC		0.15
ClinPred		0.073	T
GERP RS		0.087
Varity_R		0.046
gMVP		0.094

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs1333567790; hg19: chr1-3673423;