18-79973976-A-G

Position:

• chr18-79973976-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006701.5(TXNL4A):​c.258-120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,366,066 control chromosomes in the GnomAD database, including 671,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.96 (69947 hom., cov: 34)
  • Exomes 𝑓: 1.0 (601444 hom.)
• Consequence: TXNL4A NM_006701.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.359

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 18-79973976-A-G is Benign according to our data. Variant chr18-79973976-A-G is described in ClinVar as [Benign]. Clinvar id is 1182794.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNL4A	NM_006701.5	c.258-120T>C		intron_variant		ENST00000269601.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNL4A	ENST00000269601.10	c.258-120T>C		intron_variant		1	NM_006701.5	P1

Frequencies

GnomAD3 genomes AF: 0.956 AC: 145486 AN: 152172 Hom.: 69897 Cov.: 34

Gnomad AFR AF: 0.849

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.983

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.968

GnomAD4 exome AF: 0.995 AC: 1207985 AN: 1213776 Hom.: 601444 AF XY: 0.996 AC XY: 599359 AN XY: 601852

Gnomad4 AFR exome AF: 0.842

Gnomad4 AMR exome AF: 0.989

Gnomad4 ASJ exome AF: 0.987

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.989

GnomAD4 genome AF: 0.956 AC: 145592 AN: 152290 Hom.: 69947 Cov.: 34 AF XY: 0.957 AC XY: 71289 AN XY: 74474

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.983

Gnomad4 ASJ AF: 0.988

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.969

Alfa AF: 0.982 Hom.: 24594

Bravo AF: 0.949

Asia WGS AF: 0.992 AC: 3448 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.095
DANN	Benign	0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs4799114; hg19: chr18-77733976;