rs754716841

Variant names:

• chr11-67631611-G-A
• rs754716841
• NM_005995.5:c.1152C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-67631611-G-A
• chr11-67631611-G-T

Variant summary

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

The NM_005995.5(TBX10):​c.1152C>T​(p.Ser384Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,444,012 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. S384S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TBX10 NM_005995.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 0 publications found

Genes affected

TBX10 (HGNC:11593): (T-box transcription factor 10) This gene encodes a member of the T-box family of transcription factors. These transcription factors share a DNA-binding domain called the T-box, and play a role in several developmental processes including early embryonic cell fate and organogenesis. The encoded protein is a member of the T-box 1 subfamily. Mutations in this gene are thought to be a cause of isolated cleft lip with or without cleft palate. [provided by RefSeq, Nov 2010]

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=-0.92).
• BP7: Synonymous conserved (PhyloP=-1.57 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX10	NM_005995.5	c.1152C>T	p.Ser384Ser	synonymous_variant	Exon 8 of 8	ENST00000335385.4	NP_005986.2
TBX10	XM_047426879.1	c.2025C>T	p.Ser675Ser	synonymous_variant	Exon 11 of 11		XP_047282835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX10	ENST00000335385.4	c.1152C>T	p.Ser384Ser	synonymous_variant	Exon 8 of 8	1	NM_005995.5	ENSP00000335191.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 222696 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 AF: 0.00000208 AC: 3 AN: 1444012 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 717304

African (AFR) AF: 0.0000900 AC: 3 AN: 33316

American (AMR) AF: 0.00 AC: 0 AN: 43114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25770

East Asian (EAS) AF: 0.00 AC: 0 AN: 39378

South Asian (SAS) AF: 0.00 AC: 0 AN: 83880

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4262

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107882

Other (OTH) AF: 0.00 AC: 0 AN: 59782

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.36
DANN	Benign	0.57
PhyloP100		-1.6

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: rs754716841; hg19: chr11-67399082;