NM_006701.5:c.153+1837A>T

Variant names:

• chr18-79986403-T-A
• rs11663328
• NM_006701.5:c.153+1837A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006701.5(TXNL4A):​c.153+1837A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 151,974 control chromosomes in the GnomAD database, including 6,856 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (6856 hom., cov: 32)
• Consequence: TXNL4A NM_006701.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.344
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 18-79986403-T-A is Benign according to our data. Variant chr18-79986403-T-A is described in ClinVar as Benign. ClinVar VariationId is 1259977.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 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+1837A>T		intron	N/A	NP_006692.1	P83876
	TXNL4A	NM_001305557.2		c.129+1861A>T		intron	N/A	NP_001292486.1
	TXNL4A	NM_001303471.3		c.36+199A>T		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+1837A>T		intron	N/A	ENSP00000269601.4	P83876
	TXNL4A	ENST00000585474.5	TSL:1	c.-60-8702A>T		intron	N/A	ENSP00000465572.1	K7ESL1
	TXNL4A	ENST00000355491.5	TSL:1	n.153+1837A>T		intron	N/A	ENSP00000347678.4	O14835

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42226 AN: 151856 Hom.: 6856 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.278 AC: 42229 AN: 151974 Hom.: 6856 Cov.: 32 AF XY: 0.276 AC XY: 20507 AN XY: 74272

African (AFR) AF: 0.139 AC: 5750 AN: 41496

American (AMR) AF: 0.234 AC: 3567 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1061 AN: 3472

East Asian (EAS) AF: 0.165 AC: 851 AN: 5164

South Asian (SAS) AF: 0.152 AC: 728 AN: 4802

European-Finnish (FIN) AF: 0.358 AC: 3772 AN: 10522

Middle Eastern (MID) AF: 0.214 AC: 62 AN: 290

European-Non Finnish (NFE) AF: 0.376 AC: 25574 AN: 67958

Other (OTH) AF: 0.277 AC: 583 AN: 2108

Alfa AF: 0.317 Hom.: 1010

Bravo AF: 0.264

Asia WGS AF: 0.146 AC: 508 AN: 3476

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
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.7
DANN	Benign	0.70
PhyloP100		0.34
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: rs11663328; hg19: chr18-77746403;