chrX-103609426-C-T

Variant names:

• chrX-103609426-C-T
• rs1355402496
• NM_032926.3:c.362C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032926.3(TCEAL3):​c.362C>T​(p.Ser121Phe) 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 1,098,221 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign 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. S121Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: TCEAL3 NM_032926.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 0 publications found

Genes affected

TCEAL3 (HGNC:28247): (transcription elongation factor A like 3) This gene encodes a member of the transcription elongation factor A (SII)-like (TCEAL) gene family. Members of this family contain TFA domains and may function as nuclear phosphoproteins that modulate transcription in a promoter context-dependent manner. Multiple family members are located on the X chromosome. Alternative splicing results in multiple transcript variants encoding a single isoform. [provided by RefSeq, Jul 2008]

ENSG00000304280 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15280077).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032926.3. 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
	TCEAL3	NM_032926.3	MANE Select	c.362C>T	p.Ser121Phe	missense	Exon 3 of 3	NP_116315.1	Q969E4
	TCEAL3	NM_001006933.2		c.362C>T	p.Ser121Phe	missense	Exon 3 of 3	NP_001006934.1	Q969E4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEAL3	ENST00000372627.10	TSL:1 MANE Select	c.362C>T	p.Ser121Phe	missense	Exon 3 of 3	ENSP00000361710.5	Q969E4
	TCEAL3	ENST00000243286.7	TSL:1	c.362C>T	p.Ser121Phe	missense	Exon 3 of 3	ENSP00000243286.3	Q969E4
	TCEAL3	ENST00000372628.5	TSL:5	c.362C>T	p.Ser121Phe	missense	Exon 3 of 3	ENSP00000361711.1	Q969E4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098221 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363585

African (AFR) AF: 0.00 AC: 0 AN: 26397

American (AMR) AF: 0.00 AC: 0 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

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

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54149

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4127

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842130

Other (OTH) AF: 0.00 AC: 0 AN: 46088

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.064
Sift	Benign	0.035	D
Sift4G	Benign	0.080	T
Polyphen		1.0	D
Vest4		0.19
MutPred		0.40		Loss of phosphorylation at S121 (P = 0.0016)
MVP		0.10
MPC		1.3
ClinPred		0.44	T
GERP RS		3.7
Varity_R		0.16
gMVP		0.036
Mutation Taster		=98/2	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: rs1355402496; hg19: chrX-102864354; COSMIC: COSV105030971;