chr18-79977810-TTTTTG-T

Variant names:

• chr18-79977810-TTTTTG-T
• rs147014161
• NM_006701.5:c.154-114_154-110delCAAAA

Variant summary

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

The NM_006701.5(TXNL4A):​c.154-114_154-110delCAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 718,454 control chromosomes in the GnomAD database, including 49,320 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (9639 hom., cov: 0)
  • Exomes 𝑓: 0.36 (39681 hom.)
• Consequence: TXNL4A NM_006701.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.732
• 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, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP6: Variant 18-79977810-TTTTTG-T is Benign according to our data. Variant chr18-79977810-TTTTTG-T is described in ClinVar as Benign. ClinVar VariationId is 1258632.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.484 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.154-114_154-110delCAAAA		intron	N/A	NP_006692.1	P83876
	TXNL4A	NM_001305557.2		c.130-114_130-110delCAAAA		intron	N/A	NP_001292486.1
	TXNL4A	NM_001303471.3		c.37-114_37-110delCAAAA		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.154-114_154-110delCAAAA		intron	N/A	ENSP00000269601.4	P83876
	TXNL4A	ENST00000585474.5	TSL:1	c.-60-114_-60-110delCAAAA		intron	N/A	ENSP00000465572.1	K7ESL1
	TXNL4A	ENST00000355491.5	TSL:1	n.154-114_154-110delCAAAA		intron	N/A	ENSP00000347678.4	O14835

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52730 AN: 151292 Hom.: 9636 Cov.: 0

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.346

GnomAD4 exome AF: 0.356 AC: 201893 AN: 567046 Hom.: 39681 AF XY: 0.360 AC XY: 108393 AN XY: 301124

African (AFR) AF: 0.256 AC: 3699 AN: 14442

American (AMR) AF: 0.515 AC: 10525 AN: 20436

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 4665 AN: 15990

East Asian (EAS) AF: 0.478 AC: 15409 AN: 32220

South Asian (SAS) AF: 0.474 AC: 23963 AN: 50552

European-Finnish (FIN) AF: 0.429 AC: 17841 AN: 41556

Middle Eastern (MID) AF: 0.276 AC: 758 AN: 2746

European-Non Finnish (NFE) AF: 0.319 AC: 114496 AN: 359170

Other (OTH) AF: 0.352 AC: 10537 AN: 29934

GnomAD4 genome AF: 0.348 AC: 52752 AN: 151408 Hom.: 9639 Cov.: 0 AF XY: 0.357 AC XY: 26375 AN XY: 73930

African (AFR) AF: 0.268 AC: 11063 AN: 41328

American (AMR) AF: 0.461 AC: 6996 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1021 AN: 3464

East Asian (EAS) AF: 0.473 AC: 2420 AN: 5116

South Asian (SAS) AF: 0.501 AC: 2396 AN: 4784

European-Finnish (FIN) AF: 0.449 AC: 4688 AN: 10442

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23019 AN: 67808

Other (OTH) AF: 0.349 AC: 734 AN: 2104

Alfa AF: 0.346 Hom.: 1161

Bravo AF: 0.345

Asia WGS AF: 0.516 AC: 1791 AN: 3478

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		0.73
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs147014161; hg19: chr18-77737810; COSMIC: COSV54099374;