11-85664640-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039618.4(CREBZF):c.236C>A(p.Ser79Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,457,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CREBZF NM_001039618.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13

Genes affected

CREBZF (HGNC:24905): (CREB/ATF bZIP transcription factor) Enables identical protein binding activity. Involved in negative regulation of gene expression, epigenetic; regulation of transcription, DNA-templated; and response to virus. Located in mitochondrion and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17611381).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREBZF	NM_001039618.4	c.236C>A	p.Ser79Tyr	missense_variant	1/1	ENST00000527447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREBZF	ENST00000527447.2	c.236C>A	p.Ser79Tyr	missense_variant	1/1		NM_001039618.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000409 AC: 1 AN: 244402 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133230

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: 0.00000905

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1457094 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 724526

Gnomad4 AFR exome AF: 0.0000601

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: 0.00000180

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

Feb 10, 2022

The c.236C>A (p.S79Y) alteration is located in exon 1 (coding exon 1) of the CREBZF gene. This alteration results from a C to A substitution at nucleotide position 236, causing the serine (S) at amino acid position 79 to be replaced by a tyrosine (Y). 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	Benign	0.20
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
Cadd	Uncertain	24
Dann	Uncertain	0.98
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.065
Eigen_PC	Benign	0.041
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.047
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.024	D
Polyphen		0.62	P
Vest4		0.23
MutPred		0.15		Loss of phosphorylation at S79 (P = 0.0467);
MVP		0.12
MPC		1.4
ClinPred		0.73	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.24

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: rs954684507; hg19: chr11-85375684;