18-79986442-C-CA

Variant names:

• chr18-79986442-C-CA
• rs35507372
• NM_006701.5:c.153+1797dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006701.5(TXNL4A):​c.153+1797dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (13034 hom., cov: 0)
• Consequence: TXNL4A NM_006701.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.03
• Publications: 1 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, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 18-79986442-C-CA is Benign according to our data. Variant chr18-79986442-C-CA is described in ClinVar as Benign. ClinVar VariationId is 1288525.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

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+1797dupT		intron	N/A	NP_006692.1	P83876
	TXNL4A	NM_001305557.2		c.129+1821dupT		intron	N/A	NP_001292486.1
	TXNL4A	NM_001303471.3		c.36+159dupT		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+1797_153+1798insT		intron	N/A	ENSP00000269601.4	P83876
	TXNL4A	ENST00000585474.5	TSL:1	c.-60-8742_-60-8741insT		intron	N/A	ENSP00000465572.1	K7ESL1
	TXNL4A	ENST00000355491.5	TSL:1	n.153+1797_153+1798insT		intron	N/A	ENSP00000347678.4	O14835

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59166 AN: 151510 Hom.: 13037 Cov.: 0

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.407

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.390 AC: 59166 AN: 151630 Hom.: 13034 Cov.: 0 AF XY: 0.389 AC XY: 28785 AN XY: 74070

African (AFR) AF: 0.188 AC: 7773 AN: 41368

American (AMR) AF: 0.359 AC: 5467 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1548 AN: 3470

East Asian (EAS) AF: 0.431 AC: 2225 AN: 5160

South Asian (SAS) AF: 0.354 AC: 1703 AN: 4806

European-Finnish (FIN) AF: 0.441 AC: 4608 AN: 10448

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34382 AN: 67834

Other (OTH) AF: 0.408 AC: 859 AN: 2106

Alfa AF: 0.232 Hom.: 487

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs35507372; hg19: chr18-77746442;