NM_153035.3:c.23C>A

Variant names:

• chr1-54054445-C-A
• rs1657701657
• NM_153035.3:c.23C>A

Variant summary

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

The NM_153035.3(TCEANC2):​c.23C>A​(p.Thr8Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TCEANC2 NM_153035.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55
• Publications: 0 publications found

Genes affected

TCEANC2 (HGNC:26494): (transcription elongation factor A N-terminal and central domain containing 2) Predicted to be involved in transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.13409108).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153035.3. 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
	TCEANC2	NM_153035.3	MANE Select	c.23C>A	p.Thr8Lys	missense	Exon 2 of 5	NP_694580.1	Q96MN5-1
	TCEANC2	NR_130900.2		n.216C>A		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEANC2	ENST00000234827.6	TSL:1 MANE Select	c.23C>A	p.Thr8Lys	missense	Exon 2 of 5	ENSP00000234827.1	Q96MN5-1
	TCEANC2	ENST00000371331.1	TSL:2	c.113C>A	p.Thr38Lys	missense	Exon 1 of 4	ENSP00000360382.1	X6R7X0
	TCEANC2	ENST00000858858.1		c.23C>A	p.Thr8Lys	missense	Exon 2 of 5	ENSP00000528917.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461842 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

⚠️ 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: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60392

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

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	0.087
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.83
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.82	L
PhyloP100		1.5
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.049
Sift	Benign	0.20	T
Sift4G	Benign	0.27	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.39		Gain of methylation at T8 (P = 0.0124)
MVP		0.088
MPC		0.23
ClinPred		0.83	D
GERP RS		5.1
PromoterAI		-0.0038	Neutral
Varity_R		0.15
gMVP		0.41
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1657701657; hg19: chr1-54520118;