NM_001006935.3:c.305G>A

Variant names:

• chrX-103586980-G-A
• rs758308049
• NM_001006935.3:c.305G>A

Variant summary

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

The NM_001006935.3(TCEAL4):​c.305G>A​(p.Ser102Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 1,208,929 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 0.000036 (0 hom., 2 hem., cov: 22)
  • Exomes 𝑓: 0.0000036 (0 hom. 2 hem.)
• Consequence: TCEAL4 NM_001006935.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.12
• 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=0.045969814).
• BS2: High Hemizygotes in GnomAd4 at 2 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.305G>A	p.Ser102Asn	missense	Exon 3 of 3	NP_001006936.1	A0A384NKK0
	TCEAL4	NM_001300901.2		c.734G>A	p.Ser245Asn	missense	Exon 5 of 5	NP_001287830.1	Q96EI5-2
	TCEAL4	NM_001006937.3		c.305G>A	p.Ser102Asn	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.305G>A	p.Ser102Asn	missense	Exon 3 of 3	ENSP00000421156.1	Q96EI5-1
	TCEAL4	ENST00000372629.4	TSL:1	c.734G>A	p.Ser245Asn	missense	Exon 5 of 5	ENSP00000361712.4	Q96EI5-2
	TCEAL4	ENST00000468024.5	TSL:1	c.305G>A	p.Ser102Asn	missense	Exon 3 of 3	ENSP00000421857.1	Q96EI5-1

Frequencies

GnomAD3 genomes AF: 0.0000361 AC: 4 AN: 110797 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: 0.00114

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

GnomAD4 exome AF: 0.00000364 AC: 4 AN: 1098132 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 2 AN XY: 363500

African (AFR) AF: 0.00 AC: 0 AN: 26397

American (AMR) AF: 0.00 AC: 0 AN: 35191

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19382

East Asian (EAS) AF: 0.000132 AC: 4 AN: 30203

South Asian (SAS) AF: 0.00 AC: 0 AN: 54123

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40528

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842080

Other (OTH) AF: 0.00 AC: 0 AN: 46091

GnomAD4 genome AF: 0.0000361 AC: 4 AN: 110797 Hom.: 0 Cov.: 22 AF XY: 0.0000606 AC XY: 2 AN XY: 32983

African (AFR) AF: 0.00 AC: 0 AN: 30388

American (AMR) AF: 0.00 AC: 0 AN: 10383

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2639

East Asian (EAS) AF: 0.00114 AC: 4 AN: 3516

South Asian (SAS) AF: 0.00 AC: 0 AN: 2603

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5939

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52905

Other (OTH) AF: 0.00 AC: 0 AN: 1501

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

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	0.082
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.85
DEOGEN2	Benign	0.087	T
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-3.1
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.0040
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.038	D
Polyphen		0.32	B
Vest4		0.13
MutPred		0.27		Loss of phosphorylation at S102 (P = 9e-04)
MVP		0.082
MPC		0.85
ClinPred		0.20	T
GERP RS		-0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.99
Varity_R		0.14
gMVP		0.0077
Mutation Taster		=99/1	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: rs758308049; hg19: chrX-102841908;