rs76963654

Variant names:

• chr10-124989578-C-A
• rs76963654
• NM_001329.4:c.1278G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-124989578-C-A
• chr10-124989578-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001329.4(CTBP2):​c.1278G>T​(p.Ala426Ala) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A426A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CTBP2 NM_001329.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• Publications: 4 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=-0.068 with no splicing effect.

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.1278G>T	p.Ala426Ala	synonymous	Exon 11 of 11	NP_001320.1	P56545-1
	CTBP2	NM_022802.3		c.2898G>T	p.Ala966Ala	synonymous	Exon 9 of 9	NP_073713.2	P56545-2
	CTBP2	NM_001363508.2		c.1482G>T	p.Ala494Ala	synonymous	Exon 9 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.1278G>T	p.Ala426Ala	synonymous	Exon 11 of 11	ENSP00000338615.5	P56545-1
	CTBP2	ENST00000309035.11	TSL:1	c.2898G>T	p.Ala966Ala	synonymous	Exon 9 of 9	ENSP00000311825.6	P56545-2
	CTBP2	ENST00000334808.10	TSL:1	c.1482G>T	p.Ala494Ala	synonymous	Exon 9 of 9	ENSP00000357816.5	P56545-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 175534 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	0.95
DANN	Benign	0.81
PhyloP100		-0.068

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: rs76963654; hg19: chr10-126678147;