NM_032926.3:c.510G>A

Variant names:

• chrX-103609574-G-A
• rs1315327006
• NM_032926.3:c.510G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_032926.3(TCEAL3):​c.510G>A​(p.Gln170Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,209,664 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000020 (0 hom. 1 hem.)
• Consequence: TCEAL3 NM_032926.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.21
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant X-103609574-G-A is Benign according to our data. Variant chrX-103609574-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2661099.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.21 with no splicing effect.

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.510G>A	p.Gln170Gln	synonymous	Exon 3 of 3	NP_116315.1	Q969E4
	TCEAL3	NM_001006933.2		c.510G>A	p.Gln170Gln	synonymous	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.510G>A	p.Gln170Gln	synonymous	Exon 3 of 3	ENSP00000361710.5	Q969E4
	TCEAL3	ENST00000243286.7	TSL:1	c.510G>A	p.Gln170Gln	synonymous	Exon 3 of 3	ENSP00000243286.3	Q969E4
	TCEAL3	ENST00000372628.5	TSL:5	c.510G>A	p.Gln170Gln	synonymous	Exon 3 of 3	ENSP00000361711.1	Q969E4

Frequencies

GnomAD3 genomes AF: 0.00000898 AC: 1 AN: 111404 Hom.: 0 Cov.: 23

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: 0.0000189

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000218 AC: 4 AN: 183531 AF XY: 0.00

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: 0.0000488

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000200 AC: 22 AN: 1098260 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363616

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

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.00 AC: 0 AN: 35207

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: 0.0000261 AC: 22 AN: 842140

Other (OTH) AF: 0.00 AC: 0 AN: 46098

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000014949), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000898 AC: 1 AN: 111404 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33562

African (AFR) AF: 0.00 AC: 0 AN: 30585

American (AMR) AF: 0.00 AC: 0 AN: 10539

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3530

South Asian (SAS) AF: 0.00 AC: 0 AN: 2627

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 53034

Other (OTH) AF: 0.00 AC: 0 AN: 1502

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	4.0
DANN	Benign	0.64
PhyloP100		1.2

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: rs1315327006; hg19: chrX-102864502;