rs755516505

Variant names:

• chr19-4154920-A-C
• rs755516505
• NM_032607.3:c.49A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-4154920-A-C
• chr19-4154920-A-G

Variant summary

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

The NM_032607.3(CREB3L3):​c.49A>C​(p.Met17Leu) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: CREB3L3 NM_032607.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

Genes affected

CREB3L3 (HGNC:18855): (cAMP responsive element binding protein 3 like 3) This gene encodes a member of the basic-leucine zipper family and the AMP-dependent transcription factor family. The encoded protein is localized to the endoplasmic reticulum and acts as a transcription factor activated by cyclic AMP stimulation. The encoded protein binds the cyclic AMP response element (CRE) and the box-B element and has been linked to acute inflammatory response, hepatocellular carcinoma, triglyceride metabolism, and hepcidin expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

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=0.13799864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB3L3	NM_032607.3	c.49A>C	p.Met17Leu	missense_variant	Exon 2 of 10	ENST00000078445.7	NP_115996.1
CREB3L3	NM_001271995.2	c.49A>C	p.Met17Leu	missense_variant	Exon 2 of 10		NP_001258924.1
CREB3L3	NM_001271996.2	c.49A>C	p.Met17Leu	missense_variant	Exon 2 of 10		NP_001258925.1
CREB3L3	NM_001271997.2	c.49A>C	p.Met17Leu	missense_variant	Exon 2 of 9		NP_001258926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB3L3	ENST00000078445.7	c.49A>C	p.Met17Leu	missense_variant	Exon 2 of 10	1	NM_032607.3	ENSP00000078445.1
CREB3L3	ENST00000595923.5	c.49A>C	p.Met17Leu	missense_variant	Exon 2 of 10	1		ENSP00000469355.1
CREB3L3	ENST00000602257.5	c.49A>C	p.Met17Leu	missense_variant	Exon 2 of 10	1		ENSP00000472399.1
CREB3L3	ENST00000602147.1	c.49A>C	p.Met17Leu	missense_variant	Exon 2 of 9	1		ENSP00000470119.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 152184 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000657 AC: 1 AN: 152302 Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1 AN XY: 74484

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.0010
DANN	Benign	0.71
DEOGEN2	Benign	0.13	T;.;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.35	T;T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L;L;L;L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.1	N;.;.;.
REVEL	Benign	0.061
Sift	Benign	0.12	T;.;.;.
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;B;.;.
Vest4		0.21
MutPred		0.30		Loss of catalytic residue at M17 (P = 0.0048);Loss of catalytic residue at M17 (P = 0.0048);Loss of catalytic residue at M17 (P = 0.0048);Loss of catalytic residue at M17 (P = 0.0048);
MVP		0.49
MPC		0.093
ClinPred		0.098	T
GERP RS		-6.5
Varity_R		0.13
gMVP		0.13

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: rs755516505; hg19: chr19-4154917;