3-177038116-A-G

Variant names:

• chr3-177038116-A-G
• rs556290275
• NM_024665.7:c.1104T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024665.7(TBL1XR1):​c.1104T>C​(p.Ser368Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,354 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S368S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TBL1XR1 NM_024665.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575
• Publications: 0 publications found

Genes affected

TBL1XR1 (HGNC:29529): (TBL1X/Y related 1) This gene is a member of the WD40 repeat-containing gene family and shares sequence similarity with transducin (beta)-like 1X-linked (TBL1X). The protein encoded by this gene is thought to be a component of both nuclear receptor corepressor (N-CoR) and histone deacetylase 3 (HDAC 3) complexes, and is required for transcriptional activation by a variety of transcription factors. Mutations in these gene have been associated with some autism spectrum disorders, and one finding suggests that haploinsufficiency of this gene may be a cause of intellectual disability with dysmorphism. Mutations in this gene as well as recurrent translocations involving this gene have also been observed in some tumors. [provided by RefSeq, Mar 2016]

TBL1XR1-AS1 (HGNC:41243): (TBL1XR1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=0.575 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024665.7. 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
	TBL1XR1	NM_024665.7	MANE Select	c.1104T>C	p.Ser368Ser	synonymous	Exon 12 of 16	NP_078941.2
	TBL1XR1	NM_001321193.3		c.1104T>C	p.Ser368Ser	synonymous	Exon 12 of 16	NP_001308122.1	Q9BZK7
	TBL1XR1	NM_001321194.3		c.1104T>C	p.Ser368Ser	synonymous	Exon 13 of 17	NP_001308123.1	Q9BZK7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBL1XR1	ENST00000457928.7	TSL:1 MANE Select	c.1104T>C	p.Ser368Ser	synonymous	Exon 12 of 16	ENSP00000413251.3	Q9BZK7
	TBL1XR1	ENST00000430069.5	TSL:1	c.1104T>C	p.Ser368Ser	synonymous	Exon 12 of 16	ENSP00000405574.1	Q9BZK7
	TBL1XR1	ENST00000352800.10	TSL:5	c.1104T>C	p.Ser368Ser	synonymous	Exon 11 of 15	ENSP00000263964.11	Q9BZK7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460354 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726468

African (AFR) AF: 0.0000299 AC: 1 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4820

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111742

Other (OTH) AF: 0.00 AC: 0 AN: 60254

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.9
DANN	Benign	0.70
PhyloP100		0.57

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: rs556290275; hg19: chr3-176755904;