rs1603180742

Variant names:

• chrX-103630112-G-A
• rs1603180742
• NM_004780.3:c.196G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-103630112-G-A
• chrX-103630112-G-T

Variant summary

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

The NM_004780.3(TCEAL1):​c.196G>A​(p.Glu66Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: TCEAL1 NM_004780.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29
• Publications: 0 publications found

Genes affected

TCEAL1 (HGNC:11616): (transcription elongation factor A like 1) This gene encodes a member of the transcription elongation factor A (SII)-like (TCEAL) gene family. Members of this family may function as nuclear phosphoproteins that modulate transcription in a promoter context-dependent manner. The encoded protein is similar to transcription elongation factor A/transcription factor SII and contains a zinc finger-like motif as well as a sequence related to the transcription factor SII Pol II-binding region. It may exert its effects via protein-protein interactions with other transcriptional regulators rather than via direct binding of DNA. 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]

TCEAL1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with gait disturbance, dysmorphic facies, and behavioral abnormalities, X-linked

  Inheritance: XL Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

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=0.13457116).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004780.3. 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
	TCEAL1	NM_004780.3	MANE Select	c.196G>A	p.Glu66Lys	missense	Exon 3 of 3	NP_004771.2	Q15170
	TCEAL1	NM_001006639.2		c.196G>A	p.Glu66Lys	missense	Exon 3 of 3	NP_001006640.1	Q15170
	TCEAL1	NM_001006640.2		c.196G>A	p.Glu66Lys	missense	Exon 3 of 3	NP_001006641.1	Q15170

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEAL1	ENST00000372625.8	TSL:1 MANE Select	c.196G>A	p.Glu66Lys	missense	Exon 3 of 3	ENSP00000361708.3	Q15170
	TCEAL1	ENST00000372624.3	TSL:1	c.196G>A	p.Glu66Lys	missense	Exon 3 of 3	ENSP00000361707.3	Q15170
	TCEAL1	ENST00000469820.1	TSL:1	n.661G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	23
DANN	Uncertain	1.0
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.3
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.016
Sift	Uncertain	0.022	D
Sift4G	Benign	0.45	T
Polyphen		0.0040	B
Vest4		0.13
MutPred		0.39		Gain of methylation at E66 (P = 0.0024)
MVP		0.63
MPC		1.0
ClinPred		0.64	D
GERP RS		2.8
gMVP		0.46
Mutation Taster		=97/3	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: rs1603180742; hg19: chrX-102885040;