chr9-14720352-A-G

Position:

• chr9-14720352-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005454.3(CER1):​c.542T>C​(p.Val181Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CER1 NM_005454.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.77

Genes affected

CER1 (HGNC:1862): (cerberus 1, DAN family BMP antagonist) This gene encodes a cytokine member of the cysteine knot superfamily, characterized by nine conserved cysteines and a cysteine knot region. The cerberus-related cytokines, together with Dan and DRM/Gremlin, represent a group of bone morphogenetic protein (BMP) antagonists that can bind directly to BMPs and inhibit their activity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.884

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CER1	NM_005454.3	c.542T>C	p.Val181Ala	missense_variant	2/2	ENST00000380911.4	NP_005445.1
CER1	XR_001746419.2	n.603T>C		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CER1	ENST00000380911.4	c.542T>C	p.Val181Ala	missense_variant	2/2	1	NM_005454.3	ENSP00000370297	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460714 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726498

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 15, 2024

The c.542T>C (p.V181A) alteration is located in exon 2 (coding exon 2) of the CER1 gene. This alteration results from a T to C substitution at nucleotide position 542, causing the valine (V) at amino acid position 181 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.9	M
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.29
Sift	Benign	0.033	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.83	P
Vest4		0.64
MutPred		0.75		Loss of sheet (P = 0.0457);
MVP		0.49
MPC		0.019
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.54
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-14720350;