X-102140913-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001006938.3(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.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: TCEAL6 NM_001006938.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.929

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL6	NM_001006938.3	c.419T>A	p.Met140Lys	missense_variant	Exon 3 of 3		NP_001006939.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEAL6	ENST00000372774.8	c.419T>A	p.Met140Lys	missense_variant	Exon 3 of 4	1		ENSP00000361860.4
TCEAL6	ENST00000372773.2	c.419T>A	p.Met140Lys	missense_variant	Exon 3 of 4	3		ENSP00000361859.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.00000545 AC: 1 AN: 183339 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67841

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 SAS 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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

Alfa AF: 0.0000508 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D;D
Sift4G	Benign	1.0	T;T
Polyphen		0.98	D;D
Vest4		0.60
MutPred		0.54		Gain of ubiquitination at M140 (P = 0.0016);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

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: rs781937538; hg19: chrX-101395885;