ENST00000372774.8:c.419T>A

Variant names:

• chrX-102140913-A-T
• rs781937538
• ENST00000372774.8:c.419T>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000372774.8(TCEAL6):​c.419T>A​(p.Met140Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,144 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M140T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: TCEAL6 ENST00000372774.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.929
• Publications: 0 publications found

Genes affected

TCEAL6 (HGNC:24553): (transcription elongation factor A like 6) Predicted to enable WW domain binding activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.778

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000372774.8. 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
	TCEAL6	NM_001006938.3		c.419T>A	p.Met140Lys	missense	Exon 3 of 3	NP_001006939.2	Q6IPX3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEAL6	ENST00000372774.8	TSL:1	c.419T>A	p.Met140Lys	missense	Exon 3 of 4	ENSP00000361860.4	Q6IPX3
	TCEAL6	ENST00000372773.2	TSL:3	c.419T>A	p.Met140Lys	missense	Exon 3 of 4	ENSP00000361859.2	Q6IPX3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.00000545 AC: 1 AN: 183339 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098144 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 363554

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26394

American (AMR) AF: 0.00 AC: 0 AN: 35201

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54141

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4105

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 842095

Other (OTH) AF: 0.00 AC: 0 AN: 46083

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 24

Alfa AF: 0.0000508 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	0.98
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0044	T
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.93
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D
Sift4G	Benign	1.0	T
Polyphen		0.98	D
Vest4		0.60
MutPred		0.54		Gain of ubiquitination at M140 (P = 0.0016)
MVP		0.84
MPC		0.79
ClinPred		0.91	D
GERP RS		3.0
gMVP		0.078
Mutation Taster		=99/1	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: rs781937538; hg19: chrX-101395885;