X-103609637-G-C

Variant names:

• chrX-103609637-G-C
• rs74490974
• NM_032926.3:c.573G>C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_032926.3(TCEAL3):​c.573G>C​(p.Gln191His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000326 in 919,993 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000033 (0 hom. 4 hem.)
• Consequence: TCEAL3 NM_032926.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0500

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1271345).
• BS2: High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL3	NM_032926.3	c.573G>C	p.Gln191His	missense_variant	Exon 3 of 3	ENST00000372627.10	NP_116315.1
TCEAL3	NM_001006933.2	c.573G>C	p.Gln191His	missense_variant	Exon 3 of 3		NP_001006934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEAL3	ENST00000372627.10	c.573G>C	p.Gln191His	missense_variant	Exon 3 of 3	1	NM_032926.3	ENSP00000361710.5
TCEAL3	ENST00000243286.7	c.573G>C	p.Gln191His	missense_variant	Exon 3 of 3	1		ENSP00000243286.3
TCEAL3	ENST00000372628.5	c.573G>C	p.Gln191His	missense_variant	Exon 3 of 3	5		ENSP00000361711.1
TCEAL3	ENST00000477014.1	n.159-874G>C		intron_variant	Intron 2 of 6	5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.0000326 AC: 30 AN: 919993 Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 4 AN XY: 293395

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: 0.0000435

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.573G>C (p.Q191H) alteration is located in exon 3 (coding exon 1) of the TCEAL3 gene. This alteration results from a G to C substitution at nucleotide position 573, causing the glutamine (Q) at amino acid position 191 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.039	T;T;T
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.70	.;T;.
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.052	T;T;T
Polyphen		0.013	B;B;B
Vest4		0.35
MutPred		0.22		Gain of catalytic residue at Q191 (P = 0.0565);Gain of catalytic residue at Q191 (P = 0.0565);Gain of catalytic residue at Q191 (P = 0.0565);
MVP		0.35
MPC		0.82
ClinPred		0.16	T
GERP RS		-2.0
Varity_R		0.15
gMVP		0.036

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: rs74490974; hg19: chrX-102864565;