rs145686670

Variant names:

• chr3-107377921-A-C
• rs145686670
• NM_032600.3:c.334A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-107377921-A-C
• chr3-107377921-A-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032600.3(CCDC54):​c.334A>C​(p.Met112Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000581 in 1,614,180 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

• Frequency:
  • Genomes: 𝑓 0.00046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00059 (0 hom.)
• Consequence: CCDC54 NM_032600.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0160
• Publications: 3 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008986205).

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.334A>C	p.Met112Leu	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.334A>C	p.Met112Leu	missense	Exon 1 of 1	ENSP00000261058.1	Q8NEL0
	CCDC54-AS1	ENST00000593837.1	TSL:5	n.23+2664T>G		intron	N/A
	CCDC54-AS1	ENST00000595232.2	TSL:5	n.488+2664T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000460 AC: 70 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000339 AC: 85 AN: 251106 AF XY: 0.000332

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000608

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000594 AC: 868 AN: 1461836 Hom.: 0 Cov.: 33 AF XY: 0.000568 AC XY: 413 AN XY: 727220

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.000492 AC: 22 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000738 AC: 821 AN: 1111996

Other (OTH) AF: 0.000364 AC: 22 AN: 60392

GnomAD4 genome AF: 0.000459 AC: 70 AN: 152344 Hom.: 0 Cov.: 32 AF XY: 0.000456 AC XY: 34 AN XY: 74522

African (AFR) AF: 0.0000962 AC: 4 AN: 41572

American (AMR) AF: 0.000915 AC: 14 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000735 AC: 50 AN: 68040

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000493 Hom.: 0

Bravo AF: 0.000446

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000296 AC: 36

EpiCase AF: 0.000818

EpiControl AF: 0.000771

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	0.21
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.5
DANN	Benign	0.62
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.0090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.016
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.016
Sift	Benign	0.12	T
Sift4G	Benign	0.18	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.14		Loss of disorder (P = 0.0865)
MVP		0.092
MPC		0.035
ClinPred		0.028	T
GERP RS		1.6
PromoterAI		0.0052	Neutral
Varity_R		0.085
gMVP		0.11
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs145686670; hg19: chr3-107096768;