X-103587114-G-A

Variant names:

• chrX-103587114-G-A
• rs758997247
• NM_001006935.3:c.439G>A

Variant summary

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

The NM_001006935.3(TCEAL4):​c.439G>A​(p.Asp147Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 1,209,386 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.0000027 (0 hom. 0 hem.)
• Consequence: TCEAL4 NM_001006935.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.55
• 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: 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=0.14748257).

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.439G>A	p.Asp147Asn	missense	Exon 3 of 3	NP_001006936.1	A0A384NKK0
	TCEAL4	NM_001300901.2		c.868G>A	p.Asp290Asn	missense	Exon 5 of 5	NP_001287830.1	Q96EI5-2
	TCEAL4	NM_001006937.3		c.439G>A	p.Asp147Asn	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.439G>A	p.Asp147Asn	missense	Exon 3 of 3	ENSP00000421156.1	Q96EI5-1
	TCEAL4	ENST00000372629.4	TSL:1	c.868G>A	p.Asp290Asn	missense	Exon 5 of 5	ENSP00000361712.4	Q96EI5-2
	TCEAL4	ENST00000468024.5	TSL:1	c.439G>A	p.Asp147Asn	missense	Exon 3 of 3	ENSP00000421857.1	Q96EI5-1

Frequencies

GnomAD3 genomes AF: 0.0000448 AC: 5 AN: 111704 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000947

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000550 AC: 1 AN: 181871 AF XY: 0.0000150

Gnomad AFR exome AF: 0.0000769

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1097682 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363138

African (AFR) AF: 0.000114 AC: 3 AN: 26334

American (AMR) AF: 0.00 AC: 0 AN: 35104

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19349

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54019

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841956

Other (OTH) AF: 0.00 AC: 0 AN: 46064

GnomAD4 genome AF: 0.0000448 AC: 5 AN: 111704 Hom.: 0 Cov.: 23 AF XY: 0.0000295 AC XY: 1 AN XY: 33870

African (AFR) AF: 0.000131 AC: 4 AN: 30643

American (AMR) AF: 0.0000947 AC: 1 AN: 10564

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3572

South Asian (SAS) AF: 0.00 AC: 0 AN: 2675

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6052

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53129

Other (OTH) AF: 0.00 AC: 0 AN: 1504

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000165 AC: 2

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	0.26
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.5
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.063
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.27
MutPred		0.50		Gain of MoRF binding (P = 0.0948)
MVP		0.39
MPC		0.62
ClinPred		0.48	T
GERP RS		3.1
Varity_R		0.25
gMVP		0.029
Mutation Taster		=93/7	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: rs758997247; hg19: chrX-102842042;