NM_003196.3:c.966+491T>C

Variant names:

• chr1-23386782-A-G
• rs1198444
• NM_003196.3:c.966+491T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003196.3(TCEA3):​c.966+491T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 151,582 control chromosomes in the GnomAD database, including 58,350 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.88 (58350 hom., cov: 28)
• Consequence: TCEA3 NM_003196.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.746
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEA3	NM_003196.3	MANE Select	c.966+491T>C		intron	N/A	NP_003187.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEA3	ENST00000450454.7	TSL:1 MANE Select	c.966+491T>C		intron	N/A	ENSP00000406293.2
	TCEA3	ENST00000476978.3	TSL:3	c.966+491T>C		intron	N/A	ENSP00000474530.3

Frequencies

GnomAD3 genomes AF: 0.875 AC: 132559 AN: 151464 Hom.: 58321 Cov.: 28

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.910

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.888

Gnomad NFE AF: 0.916

Gnomad OTH AF: 0.873

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.875 AC: 132638 AN: 151582 Hom.: 58350 Cov.: 28 AF XY: 0.876 AC XY: 64909 AN XY: 74082

African (AFR) AF: 0.773 AC: 31858 AN: 41220

American (AMR) AF: 0.910 AC: 13873 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.952 AC: 3302 AN: 3468

East Asian (EAS) AF: 0.910 AC: 4668 AN: 5130

South Asian (SAS) AF: 0.827 AC: 3964 AN: 4796

European-Finnish (FIN) AF: 0.942 AC: 9899 AN: 10506

Middle Eastern (MID) AF: 0.876 AC: 254 AN: 290

European-Non Finnish (NFE) AF: 0.916 AC: 62178 AN: 67908

Other (OTH) AF: 0.868 AC: 1829 AN: 2106

Alfa AF: 0.892 Hom.: 7534

Bravo AF: 0.871

Asia WGS AF: 0.835 AC: 2905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.0
DANN	Benign	0.18
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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: rs1198444; hg19: chr1-23713275;