NM_032926.3:c.155G>A

Variant names:

• chrX-103609219-G-A
• rs778940958
• NM_032926.3:c.155G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_032926.3(TCEAL3):​c.155G>A​(p.Gly52Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000909 in 1,209,800 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000091 (0 hom. 4 hem.)
• Consequence: TCEAL3 NM_032926.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.352
• Publications: 0 publications found

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]

ENSG00000304280 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14730981).
• BS2: High Hemizygotes in GnomAdExome4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032926.3. 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
	TCEAL3	NM_032926.3	MANE Select	c.155G>A	p.Gly52Glu	missense	Exon 3 of 3	NP_116315.1	Q969E4
	TCEAL3	NM_001006933.2		c.155G>A	p.Gly52Glu	missense	Exon 3 of 3	NP_001006934.1	Q969E4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEAL3	ENST00000372627.10	TSL:1 MANE Select	c.155G>A	p.Gly52Glu	missense	Exon 3 of 3	ENSP00000361710.5	Q969E4
	TCEAL3	ENST00000243286.7	TSL:1	c.155G>A	p.Gly52Glu	missense	Exon 3 of 3	ENSP00000243286.3	Q969E4
	TCEAL3	ENST00000372628.5	TSL:5	c.155G>A	p.Gly52Glu	missense	Exon 3 of 3	ENSP00000361711.1	Q969E4

Frequencies

GnomAD3 genomes AF: 0.00000896 AC: 1 AN: 111547 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000943

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: 0.0000164 AC: 3 AN: 183483 AF XY: 0.0000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000244

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000911 AC: 10 AN: 1098253 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 4 AN XY: 363607

African (AFR) AF: 0.00 AC: 0 AN: 26402

American (AMR) AF: 0.0000284 AC: 1 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54149

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.0000107 AC: 9 AN: 842136

Other (OTH) AF: 0.00 AC: 0 AN: 46097

GnomAD4 genome AF: 0.00000896 AC: 1 AN: 111547 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33703

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

American (AMR) AF: 0.0000943 AC: 1 AN: 10606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2636

East Asian (EAS) AF: 0.00 AC: 0 AN: 3525

South Asian (SAS) AF: 0.00 AC: 0 AN: 2637

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6063

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52983

Other (OTH) AF: 0.00 AC: 0 AN: 1509

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000247 AC: 3

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	0.099
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.049	T
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.35
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.058
Sift	Benign	0.29	T
Sift4G	Benign	0.54	T
Polyphen		1.0	D
Vest4		0.21
MutPred		0.38		Gain of solvent accessibility (P = 0.024)
MVP		0.35
MPC		2.2
ClinPred		0.27	T
GERP RS		2.2
Varity_R		0.15
gMVP		0.0046
Mutation Taster		=100/0	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: rs778940958; hg19: chrX-102864147; COSMIC: COSV105030965;