rs199991104

Variant names:

• chr1-23393929-C-G
• rs199991104
• NM_003196.3:c.769G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-23393929-C-G
• chr1-23393929-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003196.3(TCEA3):​c.769G>C​(p.Val257Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. V257M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TCEA3 NM_003196.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.83
• Publications: 0 publications found

Genes affected

TCEA3 (HGNC:11615): (transcription elongation factor A3) Predicted to enable DNA binding activity and zinc ion binding activity. Predicted to be involved in regulation of transcription, DNA-templated and 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.772

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003196.3. 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
	TCEA3	NM_003196.3	MANE Select	c.769G>C	p.Val257Leu	missense	Exon 8 of 11	NP_003187.1	O75764-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEA3	ENST00000450454.7	TSL:1 MANE Select	c.769G>C	p.Val257Leu	missense	Exon 8 of 11	ENSP00000406293.2	O75764-1
	TCEA3	ENST00000476978.3	TSL:3	c.769G>C	p.Val257Leu	missense	Exon 8 of 11	ENSP00000474530.3	S4R3M9
	TCEA3	ENST00000898825.1		c.1039G>C	p.Val347Leu	missense	Exon 10 of 13	ENSP00000568884.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461596 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727084

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53296

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

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111866

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.8
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.013	D
Polyphen		0.12	B
Vest4		0.71
MutPred		0.81		Loss of MoRF binding (P = 0.0962)
MVP		0.48
MPC		0.47
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.56
gMVP		0.72
Mutation Taster		=55/45	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: rs199991104; hg19: chr1-23720422;