18-79977397-C-T

Variant names:

• chr18-79977397-C-T
• rs11081576
• NM_006701.5:c.257+201G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006701.5(TXNL4A):​c.257+201G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 544,396 control chromosomes in the GnomAD database, including 178,505 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (42929 hom., cov: 33)
  • Exomes 𝑓: 0.83 (135576 hom.)
• Consequence: TXNL4A NM_006701.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.492
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 18-79977397-C-T is Benign according to our data. Variant chr18-79977397-C-T is described in ClinVar as Benign. ClinVar VariationId is 1237111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 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.257+201G>A		intron	N/A	NP_006692.1	P83876
	TXNL4A	NM_001305557.2		c.233+201G>A		intron	N/A	NP_001292486.1
	TXNL4A	NM_001303471.3		c.140+201G>A		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.257+201G>A		intron	N/A	ENSP00000269601.4	P83876
	TXNL4A	ENST00000585474.5	TSL:1	c.44+201G>A		intron	N/A	ENSP00000465572.1	K7ESL1
	TXNL4A	ENST00000355491.5	TSL:1	n.257+201G>A		intron	N/A	ENSP00000347678.4	O14835

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110964 AN: 152044 Hom.: 42925 Cov.: 33

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.731

GnomAD4 exome AF: 0.828 AC: 324713 AN: 392234 Hom.: 135576 Cov.: 3 AF XY: 0.831 AC XY: 170881 AN XY: 205720

African (AFR) AF: 0.450 AC: 4293 AN: 9544

American (AMR) AF: 0.809 AC: 9508 AN: 11746

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 9213 AN: 12530

East Asian (EAS) AF: 0.878 AC: 23688 AN: 26968

South Asian (SAS) AF: 0.875 AC: 27635 AN: 31580

European-Finnish (FIN) AF: 0.881 AC: 28099 AN: 31882

Middle Eastern (MID) AF: 0.759 AC: 1367 AN: 1800

European-Non Finnish (NFE) AF: 0.833 AC: 202343 AN: 242992

Other (OTH) AF: 0.801 AC: 18567 AN: 23192

GnomAD4 genome AF: 0.729 AC: 110999 AN: 152162 Hom.: 42929 Cov.: 33 AF XY: 0.739 AC XY: 54938 AN XY: 74386

African (AFR) AF: 0.449 AC: 18602 AN: 41454

American (AMR) AF: 0.808 AC: 12359 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2521 AN: 3472

East Asian (EAS) AF: 0.912 AC: 4729 AN: 5186

South Asian (SAS) AF: 0.882 AC: 4246 AN: 4816

European-Finnish (FIN) AF: 0.892 AC: 9457 AN: 10602

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56523 AN: 68024

Other (OTH) AF: 0.734 AC: 1548 AN: 2108

Alfa AF: 0.782 Hom.: 20331

Bravo AF: 0.707

Asia WGS AF: 0.867 AC: 3015 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.57
DANN	Benign	0.62
PhyloP100		-0.49
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: rs11081576; hg19: chr18-77737397;