18-79986623-T-C

Variant names:

• chr18-79986623-T-C
• rs8086024
• NM_006701.5:c.153+1617A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001303471.3(TXNL4A):​c.15A>G​(p.Arg5Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 985,268 control chromosomes in the GnomAD database, including 335,827 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (47656 hom., cov: 33)
  • Exomes 𝑓: 0.83 (288171 hom.)
• Consequence: TXNL4A NM_001303471.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.00600
• Publications: 16 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, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 18-79986623-T-C is Benign according to our data. Variant chr18-79986623-T-C is described in ClinVar as Benign. ClinVar VariationId is 1177803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.006 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303471.3. 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+1617A>G		intron	N/A	NP_006692.1	P83876
	TXNL4A	NM_001303471.3		c.15A>G	p.Arg5Arg	synonymous	Exon 2 of 4	NP_001290400.1
	TXNL4A	NM_001305557.2		c.129+1641A>G		intron	N/A	NP_001292486.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNL4A	ENST00000269601.10	TSL:1 MANE Select	c.153+1617A>G		intron	N/A	ENSP00000269601.4	P83876
	TXNL4A	ENST00000585474.5	TSL:1	c.-60-8922A>G		intron	N/A	ENSP00000465572.1	K7ESL1
	TXNL4A	ENST00000355491.5	TSL:1	n.153+1617A>G		intron	N/A	ENSP00000347678.4	O14835

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119430 AN: 152054 Hom.: 47630 Cov.: 33

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.884

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.777

GnomAD4 exome AF: 0.831 AC: 692345 AN: 833096 Hom.: 288171 Cov.: 52 AF XY: 0.832 AC XY: 320179 AN XY: 384708

African (AFR) AF: 0.617 AC: 9742 AN: 15786

American (AMR) AF: 0.834 AC: 821 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 3798 AN: 5152

East Asian (EAS) AF: 0.916 AC: 3324 AN: 3630

South Asian (SAS) AF: 0.873 AC: 14372 AN: 16460

European-Finnish (FIN) AF: 0.858 AC: 242 AN: 282

Middle Eastern (MID) AF: 0.778 AC: 1261 AN: 1620

European-Non Finnish (NFE) AF: 0.835 AC: 636247 AN: 761884

Other (OTH) AF: 0.826 AC: 22538 AN: 27298

GnomAD4 genome AF: 0.785 AC: 119508 AN: 152172 Hom.: 47656 Cov.: 33 AF XY: 0.791 AC XY: 58875 AN XY: 74412

African (AFR) AF: 0.643 AC: 26656 AN: 41482

American (AMR) AF: 0.828 AC: 12650 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2521 AN: 3470

East Asian (EAS) AF: 0.912 AC: 4724 AN: 5178

South Asian (SAS) AF: 0.883 AC: 4258 AN: 4824

European-Finnish (FIN) AF: 0.892 AC: 9465 AN: 10612

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56566 AN: 68004

Other (OTH) AF: 0.780 AC: 1647 AN: 2112

Alfa AF: 0.808 Hom.: 8152

Bravo AF: 0.771

Asia WGS AF: 0.881 AC: 3063 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	TXNL4A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.1
DANN	Benign	0.86
PhyloP100		0.0060
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: rs8086024; hg19: chr18-77746623;