X-103586836-G-A

Variant names:

• chrX-103586836-G-A
• rs771193166
• NM_001006935.3:c.161G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001006935.3(TCEAL4):​c.161G>A​(p.Gly54Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000916 in 1,091,313 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.0000092 (0 hom. 3 hem.)
  • Failed GnomAD Quality Control
• Consequence: TCEAL4 NM_001006935.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0340
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03633529).
• BP6: Variant X-103586836-G-A is Benign according to our data. Variant chrX-103586836-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3175055.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006935.3. 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
	TCEAL4	NM_001006935.3	MANE Select	c.161G>A	p.Gly54Glu	missense	Exon 3 of 3	NP_001006936.1	A0A384NKK0
	TCEAL4	NM_001300901.2		c.590G>A	p.Gly197Glu	missense	Exon 5 of 5	NP_001287830.1	Q96EI5-2
	TCEAL4	NM_001006937.3		c.161G>A	p.Gly54Glu	missense	Exon 3 of 3	NP_001006938.1	Q96EI5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEAL4	ENST00000472484.6	TSL:1 MANE Select	c.161G>A	p.Gly54Glu	missense	Exon 3 of 3	ENSP00000421156.1	Q96EI5-1
	TCEAL4	ENST00000372629.4	TSL:1	c.590G>A	p.Gly197Glu	missense	Exon 5 of 5	ENSP00000361712.4	Q96EI5-2
	TCEAL4	ENST00000468024.5	TSL:1	c.161G>A	p.Gly54Glu	missense	Exon 3 of 3	ENSP00000421857.1	Q96EI5-1

Frequencies

GnomAD3 genomes AF: 0.00000895 AC: 1 AN: 111701 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000241 AC: 4 AN: 166160 AF XY: 0.0000182

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: 0.0000555

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000916 AC: 10 AN: 1091313 Hom.: 0 Cov.: 31 AF XY: 0.00000838 AC XY: 3 AN XY: 357869

African (AFR) AF: 0.0000382 AC: 1 AN: 26155

American (AMR) AF: 0.00 AC: 0 AN: 34100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19302

East Asian (EAS) AF: 0.00 AC: 0 AN: 29882

South Asian (SAS) AF: 0.00 AC: 0 AN: 53211

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.0000107 AC: 9 AN: 838360

Other (OTH) AF: 0.00 AC: 0 AN: 45901

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000895 AC: 1 AN: 111701 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 33875

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

African (AFR) AF: 0.00 AC: 0 AN: 30667

American (AMR) AF: 0.00 AC: 0 AN: 10496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3561

South Asian (SAS) AF: 0.00 AC: 0 AN: 2630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6093

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53182

Other (OTH) AF: 0.00 AC: 0 AN: 1503

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000828 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.39
DEOGEN2	Benign	0.0016	T
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.17	N
PhyloP100		0.034
PrimateAI	Benign	0.31	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.038
Sift	Benign	0.47	T
Sift4G	Benign	0.80	T
Polyphen		0.0010	B
Vest4		0.055
MutPred		0.41		Gain of solvent accessibility (P = 0.012)
MVP		0.068
MPC		0.63
ClinPred		0.025	T
GERP RS		-1.4
Varity_R		0.057
gMVP		0.0047
Mutation Taster		=97/3	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: rs771193166; hg19: chrX-102841764;