rs374962229

Variant names:

• chrX-102127492-C-T
• rs374962229
• NM_080390.4:c.662C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-102127492-C-T
• chrX-102127492-C-G

Variant summary

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

The NM_080390.4(TCEAL2):​c.662C>T​(p.Thr221Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,177,270 control chromosomes in the GnomAD database, including 1 homozygotes. There are 51 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 0.00033 (1 hom., 11 hem., cov: 23)
  • Exomes 𝑓: 0.00014 (0 hom. 40 hem.)
• Consequence: TCEAL2 NM_080390.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.262
• Publications: 0 publications found

Genes affected

TCEAL2 (HGNC:29818): (transcription elongation factor A like 2) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00908795).
• BS2: High Hemizygotes in GnomAd4 at 11 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080390.4. 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
	TCEAL2	NM_080390.4	MANE Select	c.662C>T	p.Thr221Ile	missense	Exon 3 of 3	NP_525129.1	Q9H3H9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEAL2	ENST00000372780.6	TSL:1 MANE Select	c.662C>T	p.Thr221Ile	missense	Exon 3 of 3	ENSP00000361866.1	Q9H3H9
	TCEAL2	ENST00000329035.2	TSL:5	c.662C>T	p.Thr221Ile	missense	Exon 3 of 3	ENSP00000332359.2	Q9H3H9
	TCEAL2	ENST00000902218.1		c.662C>T	p.Thr221Ile	missense	Exon 3 of 3	ENSP00000572277.1

Frequencies

GnomAD3 genomes AF: 0.000332 AC: 37 AN: 111517 Hom.: 1 Cov.: 23

Gnomad AFR AF: 0.000849

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000283

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000166

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000113

Gnomad OTH AF: 0.000668

GnomAD2 exomes AF: 0.000182 AC: 27 AN: 148070 AF XY: 0.000146

Gnomad AFR exome AF: 0.000837

Gnomad AMR exome AF: 0.000622

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000431

Gnomad OTH exome AF: 0.000286

GnomAD4 exome AF: 0.000142 AC: 151 AN: 1065753 Hom.: 0 Cov.: 31 AF XY: 0.000116 AC XY: 40 AN XY: 345273

African (AFR) AF: 0.000847 AC: 21 AN: 24798

American (AMR) AF: 0.000626 AC: 18 AN: 28750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16781

East Asian (EAS) AF: 0.0000332 AC: 1 AN: 30093

South Asian (SAS) AF: 0.0000841 AC: 4 AN: 47567

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39241

Middle Eastern (MID) AF: 0.000261 AC: 1 AN: 3835

European-Non Finnish (NFE) AF: 0.000116 AC: 96 AN: 830054

Other (OTH) AF: 0.000224 AC: 10 AN: 44634

GnomAD4 genome AF: 0.000332 AC: 37 AN: 111517 Hom.: 1 Cov.: 23 AF XY: 0.000325 AC XY: 11 AN XY: 33795

African (AFR) AF: 0.000849 AC: 26 AN: 30633

American (AMR) AF: 0.000283 AC: 3 AN: 10585

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2637

East Asian (EAS) AF: 0.00 AC: 0 AN: 3557

South Asian (SAS) AF: 0.00 AC: 0 AN: 2653

European-Finnish (FIN) AF: 0.000166 AC: 1 AN: 6021

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.000113 AC: 6 AN: 53015

Other (OTH) AF: 0.000668 AC: 1 AN: 1498

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000518

ESP6500AA AF: 0.000271 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000207 AC: 25

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	0.090
BayesDel_addAF	Benign	-0.88	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	5.2
DANN	Benign	0.95
DEOGEN2	Benign	0.0028	T
FATHMM_MKL	Benign	0.00019	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.0091	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.69	N
PhyloP100		-0.26
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.037
Sift	Benign	0.80	T
Sift4G	Benign	0.52	T
Polyphen		0.0050	B
Vest4		0.072
MVP		0.043
MPC		0.10
ClinPred		0.0022	T
GERP RS		1.0
Varity_R		0.034
gMVP		0.020
Mutation Taster		=98/2	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: rs374962229; hg19: chrX-101382464;