chrX-102141291-T-C

Variant names:

• chrX-102141291-T-C
• rs202195134
• ENST00000372774.8:c.41A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001006938.3(TCEAL6):​c.41A>G​(p.Asn14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,208,484 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N14I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.0000027 (0 hom. 0 hem.)
• Consequence: TCEAL6 NM_001006938.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 0 publications found

Genes affected

TCEAL6 (HGNC:24553): (transcription elongation factor A like 6) Predicted to enable WW domain binding activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03914562).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006938.3. 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
	TCEAL6	NM_001006938.3		c.41A>G	p.Asn14Ser	missense	Exon 3 of 3	NP_001006939.2	Q6IPX3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEAL6	ENST00000372774.8	TSL:1	c.41A>G	p.Asn14Ser	missense	Exon 3 of 4	ENSP00000361860.4	Q6IPX3
	TCEAL6	ENST00000372773.2	TSL:3	c.41A>G	p.Asn14Ser	missense	Exon 3 of 4	ENSP00000361859.2	Q6IPX3

Frequencies

GnomAD3 genomes AF: 0.0000177 AC: 2 AN: 112819 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000559

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: 0.0000114 AC: 2 AN: 176068 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: 0.000150

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 3 AN: 1095615 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 361547

African (AFR) AF: 0.00 AC: 0 AN: 26105

American (AMR) AF: 0.00 AC: 0 AN: 34655

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19288

East Asian (EAS) AF: 0.0000993 AC: 3 AN: 30200

South Asian (SAS) AF: 0.00 AC: 0 AN: 53347

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4122

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841454

Other (OTH) AF: 0.00 AC: 0 AN: 45944

GnomAD4 genome AF: 0.0000177 AC: 2 AN: 112869 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 35021

African (AFR) AF: 0.00 AC: 0 AN: 31119

American (AMR) AF: 0.00 AC: 0 AN: 10772

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

East Asian (EAS) AF: 0.000561 AC: 2 AN: 3567

South Asian (SAS) AF: 0.00 AC: 0 AN: 2755

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6259

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53303

Other (OTH) AF: 0.00 AC: 0 AN: 1541

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-1.2
CADD	Benign	0.082
DANN	Benign	0.83
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.072	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.4	L
PhyloP100		-1.8
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.020
Sift	Benign	0.29	T
Sift4G	Benign	0.69	T
Polyphen		0.0010	B
Vest4		0.072
MVP		0.068
MPC		0.17
ClinPred		0.032	T
GERP RS		-1.8
gMVP		0.0048
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: rs202195134; hg19: chrX-101396263;