X-103586881-G-C

Variant names:

• chrX-103586881-G-C
• rs908212559
• NM_001006935.3:c.206G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001006935.3(TCEAL4):​c.206G>C​(p.Gly69Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,194,483 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G69R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.000034 (0 hom. 15 hem.)
• Consequence: TCEAL4 NM_001006935.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.02
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04684457).
• BS2: High Hemizygotes in GnomAdExome4 at 15 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.206G>C	p.Gly69Ala	missense	Exon 3 of 3	NP_001006936.1	A0A384NKK0
	TCEAL4	NM_001300901.2		c.635G>C	p.Gly212Ala	missense	Exon 5 of 5	NP_001287830.1	Q96EI5-2
	TCEAL4	NM_001006937.3		c.206G>C	p.Gly69Ala	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.206G>C	p.Gly69Ala	missense	Exon 3 of 3	ENSP00000421156.1	Q96EI5-1
	TCEAL4	ENST00000372629.4	TSL:1	c.635G>C	p.Gly212Ala	missense	Exon 5 of 5	ENSP00000361712.4	Q96EI5-2
	TCEAL4	ENST00000468024.5	TSL:1	c.206G>C	p.Gly69Ala	missense	Exon 3 of 3	ENSP00000421857.1	Q96EI5-1

Frequencies

GnomAD3 genomes AF: 0.0000270 AC: 3 AN: 110961 Hom.: 0 Cov.: 22

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: 0.0000567

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000655 AC: 1 AN: 152648 AF XY: 0.0000206

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: 0.0000154

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000341 AC: 37 AN: 1083522 Hom.: 0 Cov.: 31 AF XY: 0.0000424 AC XY: 15 AN XY: 353772

African (AFR) AF: 0.00 AC: 0 AN: 25890

American (AMR) AF: 0.00 AC: 0 AN: 32308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19192

East Asian (EAS) AF: 0.00 AC: 0 AN: 29392

South Asian (SAS) AF: 0.00 AC: 0 AN: 52524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39823

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4124

European-Non Finnish (NFE) AF: 0.0000347 AC: 29 AN: 834629

Other (OTH) AF: 0.000175 AC: 8 AN: 45640

GnomAD4 genome AF: 0.0000270 AC: 3 AN: 110961 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33149

African (AFR) AF: 0.00 AC: 0 AN: 30485

American (AMR) AF: 0.00 AC: 0 AN: 10417

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3507

South Asian (SAS) AF: 0.00 AC: 0 AN: 2610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5955

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000567 AC: 3 AN: 52934

Other (OTH) AF: 0.00 AC: 0 AN: 1482

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.085
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.63
DANN	Benign	0.62
DEOGEN2	Benign	0.012	T
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		-1.0
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.017
Sift	Benign	0.17	T
Sift4G	Benign	0.35	T
Polyphen		0.0	B
Vest4		0.050
MutPred		0.25		Gain of helix (P = 0.0854)
MVP		0.16
MPC		0.56
ClinPred		0.069	T
GERP RS		-4.5
Varity_R		0.070
gMVP		0.016
Mutation Taster		=96/4	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: rs908212559; hg19: chrX-102841809;