2-99306504-C-T

Variant names:

• chr2-99306504-C-T
• rs6722617
• ENST00000424491.5:n.*293-14622C>T

Variant summary

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

The ENST00000424491.5(ENSG00000241962):​n.*293-14622C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 151,494 control chromosomes in the GnomAD database, including 28,214 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 0.60 (28214 hom., cov: 32)
• Consequence: ENSG00000241962 ENST00000424491.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.652
• Publications: 4 publications found

Genes affected

ENSG00000241962 (HGNC:):

TXNDC9 (HGNC:24110): (thioredoxin domain containing 9) The protein encoded by this gene is a member of the thioredoxin family. The exact function of this protein is not known but it is associated with cell differentiation. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000424491.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000241962	ENST00000424491.5	TSL:2	n.*293-14622C>T		intron	N/A	ENSP00000390891.1

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91160 AN: 151374 Hom.: 28206 Cov.: 32

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.602 AC: 91196 AN: 151494 Hom.: 28214 Cov.: 32 AF XY: 0.601 AC XY: 44480 AN XY: 74000

African (AFR) AF: 0.465 AC: 19249 AN: 41386

American (AMR) AF: 0.648 AC: 9897 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2828 AN: 3452

East Asian (EAS) AF: 0.696 AC: 3573 AN: 5132

South Asian (SAS) AF: 0.645 AC: 3104 AN: 4814

European-Finnish (FIN) AF: 0.558 AC: 5769 AN: 10332

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44632 AN: 67802

Other (OTH) AF: 0.657 AC: 1388 AN: 2114

Alfa AF: 0.644 Hom.: 26526

Bravo AF: 0.604

Asia WGS AF: 0.646 AC: 2250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.23
PhyloP100		-0.65

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6722617;

hg19: chr2-99922967;

COSMIC: COSV68215278;