X-103587300-A-G

Variant names:

• chrX-103587300-A-G
• rs202054247
• NM_001006935.3:c.625A>G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001006935.3(TCEAL4):​c.625A>G​(p.Ile209Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,180,940 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.000059 (0 hom. 17 hem.)
• Consequence: TCEAL4 NM_001006935.3 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -0.204

Genes affected

TCEAL4 (HGNC:26121): (transcription elongation factor A like 4) This gene encodes a member of the transcription elongation factor A (SII)-like (TCEAL) gene family. This family is comprised of nuclear phosphoproteins that modulate transcription in a promoter context-dependent manner. Multiple family members are located on the X chromosome. Alternatively splicing results in multiple transcript variants. There is a pseudogene for this gene on chromosome 13. [provided by RefSeq, Apr 2015]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034282207).
• BP6: Variant X-103587300-A-G is Benign according to our data. Variant chrX-103587300-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2661098.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BS2: High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL4	NM_001006935.3	c.625A>G	p.Ile209Val	missense_variant	Exon 3 of 3	ENST00000472484.6	NP_001006936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEAL4	ENST00000472484.6	c.625A>G	p.Ile209Val	missense_variant	Exon 3 of 3	1	NM_001006935.3	ENSP00000421156.1

Frequencies

GnomAD3 genomes AF: 0.0000717 AC: 8 AN: 111554 Hom.: 0 Cov.: 23 AF XY: 0.0000593 AC XY: 2 AN XY: 33732

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000951

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000663 AC: 10 AN: 150754 Hom.: 0 AF XY: 0.0000413 AC XY: 2 AN XY: 48450

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000454

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000859

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000589 AC: 63 AN: 1069333 Hom.: 0 Cov.: 32 AF XY: 0.0000491 AC XY: 17 AN XY: 346555

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000332

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000416

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000686

Gnomad4 OTH exome AF: 0.0000446

GnomAD4 genome AF: 0.0000717 AC: 8 AN: 111607 Hom.: 0 Cov.: 23 AF XY: 0.0000592 AC XY: 2 AN XY: 33795

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000950

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000261 Hom.: 3

Bravo AF: 0.0000718

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000580 AC: 7

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Apr 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.625A>G (p.I209V) alteration is located in exon 3 (coding exon 1) of the TCEAL4 gene. This alteration results from a A to G substitution at nucleotide position 625, causing the isoleucine (I) at amino acid position 209 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TCEAL4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.93
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.013	.;T;T;T;T;T;T
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.26	T;.;.;.;T;.;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.034	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	.;L;L;L;.;L;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.52	N;N;N;N;.;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.021	D;T;T;T;.;T;T
Sift4G	Benign	0.088	T;T;T;T;T;T;T
Polyphen		0.022	.;B;B;B;.;B;B
Vest4		0.13
MVP		0.12
MPC		0.41
ClinPred		0.029	T
GERP RS		1.3
Varity_R		0.072
gMVP		0.023

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: rs202054247; hg19: chrX-102842228;