3-107377856-T-G

Variant names:

• chr3-107377856-T-G
• rs534564254
• NM_032600.3:c.269T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032600.3(CCDC54):​c.269T>G​(p.Met90Arg) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M90T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC54 NM_032600.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.191
• Publications: 0 publications found

Genes affected

CCDC54 (HGNC:30703): (coiled-coil domain containing 54)

CCDC54-AS1 (HGNC:56107): (CCDC54 antisense RNA 1)

DUBR (HGNC:48569): (DPPA2 upstream binding RNA) Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II; positive regulation of myoblast differentiation; and regulation of DNA methylation. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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 (MetaRNN=0.05232656).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032600.3. 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
	CCDC54	NM_032600.3	MANE Select	c.269T>G	p.Met90Arg	missense	Exon 1 of 1	NP_115989.1	Q8NEL0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC54	ENST00000261058.3	TSL:6 MANE Select	c.269T>G	p.Met90Arg	missense	Exon 1 of 1	ENSP00000261058.1	Q8NEL0
	CCDC54-AS1	ENST00000593837.1	TSL:5	n.23+2729A>C		intron	N/A
	CCDC54-AS1	ENST00000595232.2	TSL:5	n.488+2729A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.4
DANN	Benign	0.67
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.19
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.015
Sift	Benign	0.073	T
Sift4G	Uncertain	0.040	D
Polyphen		0.0	B
Vest4		0.14
MutPred		0.33		Gain of solvent accessibility (P = 0.0055)
MVP		0.040
MPC		0.047
ClinPred		0.049	T
GERP RS		1.3
PromoterAI		-0.016	Neutral
Varity_R		0.15
gMVP		0.098
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs534564254; hg19: chr3-107096703;