rs76079088

Variant names:

• chr10-125002969-C-A
• rs76079088
• NM_001329.4:c.349G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-125002969-C-A
• chr10-125002969-C-G
• chr10-125002969-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM5 PP3

The NM_001329.4(CTBP2):​c.349G>T​(p.Gly117Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G117S) has been classified as Pathogenic.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CTBP2 NM_001329.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.16
• Publications: 0 publications found

Genes affected

CTBP2 (HGNC:2495): (C-terminal binding protein 2) This gene produces alternative transcripts encoding two distinct proteins. One protein is a transcriptional repressor, while the other isoform is a major component of specialized synapses known as synaptic ribbons. Both proteins contain a NAD+ binding domain similar to NAD+-dependent 2-hydroxyacid dehydrogenases. A portion of the 3' untranslated region was used to map this gene to chromosome 21q21.3; however, it was noted that similar loci elsewhere in the genome are likely. Blast analysis shows that this gene is present on chromosome 10. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr10-125002969-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 1696855.Status of the report is no_assertion_criteria_provided, 0 stars.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.828

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329.4. 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
	CTBP2	NM_001329.4	MANE Select	c.349G>T	p.Gly117Cys	missense	Exon 5 of 11	NP_001320.1	P56545-1
	CTBP2	NM_022802.3		c.1969G>T	p.Gly657Cys	missense	Exon 3 of 9	NP_073713.2	P56545-2
	CTBP2	NM_001363508.2		c.553G>T	p.Gly185Cys	missense	Exon 3 of 9	NP_001350437.1	P56545-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP2	ENST00000337195.11	TSL:1 MANE Select	c.349G>T	p.Gly117Cys	missense	Exon 5 of 11	ENSP00000338615.5	P56545-1
	CTBP2	ENST00000309035.11	TSL:1	c.1969G>T	p.Gly657Cys	missense	Exon 3 of 9	ENSP00000311825.6	P56545-2
	CTBP2	ENST00000334808.10	TSL:1	c.553G>T	p.Gly185Cys	missense	Exon 3 of 9	ENSP00000357816.5	P56545-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460470 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726558

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5170

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111874

Other (OTH) AF: 0.00 AC: 0 AN: 60302

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D
Eigen	Benign	0.13
Eigen_PC	Benign	0.089
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Benign	0.88	L
PhyloP100		6.2
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-7.5	D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.025	D
Polyphen		0.64	P
Vest4		0.78
MutPred		0.57		Loss of catalytic residue at G185 (P = 0.0849)
MVP		0.90
MPC		2.0
ClinPred		1.0	D
GERP RS		3.8
Varity_R		0.97
gMVP		0.88
Mutation Taster		=22/78	disease causing

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

Other links and lift over

dbSNP: rs76079088; hg19: chr10-126691538;