chr18-79986891-T-C

Variant names:

• chr18-79986891-T-C
• rs116384147
• NM_006701.5:c.153+1349A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006701.5(TXNL4A):​c.153+1349A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 483,418 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (76 hom., cov: 33)
  • Exomes 𝑓: 0.018 (71 hom.)
• Consequence: TXNL4A NM_006701.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.01
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 18-79986891-T-C is Benign according to our data. Variant chr18-79986891-T-C is described in ClinVar as Benign. ClinVar VariationId is 1182672.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0241 (3671/152314) while in subpopulation AFR AF = 0.0478 (1985/41564). AF 95% confidence interval is 0.046. There are 76 homozygotes in GnomAd4. There are 1739 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 76 AR,Unknown gene

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+1349A>G		intron	N/A	NP_006692.1	P83876
	TXNL4A	NM_001305557.2		c.129+1373A>G		intron	N/A	NP_001292486.1
	TXNL4A	NM_001303471.3		c.-113-141A>G		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+1349A>G		intron	N/A	ENSP00000269601.4	P83876
	TXNL4A	ENST00000585474.5	TSL:1	c.-60-9190A>G		intron	N/A	ENSP00000465572.1	K7ESL1
	TXNL4A	ENST00000355491.5	TSL:1	n.153+1349A>G		intron	N/A	ENSP00000347678.4	O14835

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3662 AN: 152196 Hom.: 74 Cov.: 33

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.0181

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0179

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.0178 AC: 5895 AN: 331104 Hom.: 71 AF XY: 0.0179 AC XY: 2795 AN XY: 156476

African (AFR) AF: 0.0509 AC: 310 AN: 6086

American (AMR) AF: 0.0191 AC: 7 AN: 366

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 38 AN: 2064

East Asian (EAS) AF: 0.00 AC: 0 AN: 1278

South Asian (SAS) AF: 0.00422 AC: 27 AN: 6404

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 96

Middle Eastern (MID) AF: 0.0266 AC: 16 AN: 602

European-Non Finnish (NFE) AF: 0.0175 AC: 5304 AN: 303356

Other (OTH) AF: 0.0178 AC: 193 AN: 10852

GnomAD4 genome AF: 0.0241 AC: 3671 AN: 152314 Hom.: 76 Cov.: 33 AF XY: 0.0233 AC XY: 1739 AN XY: 74478

African (AFR) AF: 0.0478 AC: 1985 AN: 41564

American (AMR) AF: 0.0191 AC: 292 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0181 AC: 63 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4828

European-Finnish (FIN) AF: 0.00217 AC: 23 AN: 10618

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0179 AC: 1215 AN: 68032

Other (OTH) AF: 0.0331 AC: 70 AN: 2114

Alfa AF: 0.0237 Hom.: 25

Bravo AF: 0.0258

Asia WGS AF: 0.0130 AC: 45 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
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.23
DANN	Benign	0.50
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism

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: rs116384147; hg19: chr18-77746891;