18-80005220-C-T

Variant names:

• chr18-80005220-C-T
• rs12604993
• ENST00000585474.5:c.-60-27519G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000585474.5(TXNL4A):​c.-60-27519G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,168 control chromosomes in the GnomAD database, including 1,710 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1710 hom., cov: 33)
• Consequence: TXNL4A ENST00000585474.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 9 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNL4A	NM_001305563.2	c.-61+25301G>A		intron_variant	Intron 2 of 3		NP_001292492.1
TXNL4A	NM_001305564.2	c.-60-27519G>A		intron_variant	Intron 1 of 2		NP_001292493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNL4A	ENST00000585474.5	c.-60-27519G>A		intron_variant	Intron 1 of 2	1		ENSP00000465572.1
TXNL4A	ENST00000592957.1	c.-61+25301G>A		intron_variant	Intron 2 of 3	3		ENSP00000465493.1
TXNL4A	ENST00000589926.1	n.45-9787G>A		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22032 AN: 152050 Hom.: 1710 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.0852

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.145 AC: 22043 AN: 152168 Hom.: 1710 Cov.: 33 AF XY: 0.144 AC XY: 10689 AN XY: 74398

African (AFR) AF: 0.124 AC: 5142 AN: 41510

American (AMR) AF: 0.151 AC: 2316 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 560 AN: 3470

East Asian (EAS) AF: 0.270 AC: 1392 AN: 5152

South Asian (SAS) AF: 0.206 AC: 993 AN: 4816

European-Finnish (FIN) AF: 0.0852 AC: 902 AN: 10592

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10110 AN: 68016

Other (OTH) AF: 0.172 AC: 363 AN: 2116

Alfa AF: 0.0949 Hom.: 154

Bravo AF: 0.147

Asia WGS AF: 0.209 AC: 726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.34
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12604993; hg19: chr18-77765220;