rs879255559

Variant names:

• chr18-79988237-T-C
• rs879255559
• NM_006701.5:c.153+3A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006701.5(TXNL4A):​c.153+3A>G variant causes a splice region, intron 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. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TXNL4A NM_006701.5 splice_region, intron
• Scores: Splicing: ADA: 0.8933
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.496
• Publications: 0 publications found

Genes affected

TXNL4A (HGNC:30551): (thioredoxin like 4A) The protein encoded by this gene is a member of the U5 small ribonucleoprotein particle (snRNP), and is involved in pre-mRNA splicing. This protein contains a thioredoxin-like fold and it is expected to interact with multiple proteins. Protein-protein interactions have been observed with the polyglutamine tract-binding protein 1 (PQBP1). Mutations in both the coding region and promoter region of this gene have been associated with Burn-McKeown syndrome, which is a rare disorder characterized by craniofacial dysmorphisms, cardiac defects, hearing loss, and bilateral choanal atresia. A pseudogene of this gene is found on chromosome 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2015]

TXNL4A Gene-Disease associations (from GenCC):

• choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome

  Inheritance: AR, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006701.5. 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
	TXNL4A	NM_006701.5	MANE Select	c.153+3A>G		splice_region intron	N/A	NP_006692.1	P83876
	TXNL4A	NM_001305557.2		c.129+27A>G		intron	N/A	NP_001292486.1
	TXNL4A	NM_001303471.3		c.-114+3A>G		splice_region intron	N/A	NP_001290400.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNL4A	ENST00000269601.10	TSL:1 MANE Select	c.153+3A>G		splice_region intron	N/A	ENSP00000269601.4	P83876
	TXNL4A	ENST00000585474.5	TSL:1	c.-60-10536A>G		intron	N/A	ENSP00000465572.1	K7ESL1
	TXNL4A	ENST00000355491.5	TSL:1	n.153+3A>G		splice_region intron	N/A	ENSP00000347678.4	O14835

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1381352 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 681982

African (AFR) AF: 0.00 AC: 0 AN: 31236

American (AMR) AF: 0.00 AC: 0 AN: 42214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24192

East Asian (EAS) AF: 0.00 AC: 0 AN: 36894

South Asian (SAS) AF: 0.00 AC: 0 AN: 78994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5416

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1055438

Other (OTH) AF: 0.00 AC: 0 AN: 55918

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions as Germline

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	Choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.74
PhyloP100		0.50
PromoterAI		-0.25	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=7/93	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.89
dbscSNV1_RF	Benign	0.59
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.30		Position offset: 27

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs879255559; hg19: chr18-77748237;