18-9886893-A-G

Variant names:

• chr18-9886893-A-G
• rs601874
• NM_032243.6:c.213A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032243.6(TXNDC2):​c.213A>G​(p.Ser71Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,610,688 control chromosomes in the GnomAD database, including 54,552 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4343 hom., cov: 29)
  • Exomes 𝑓: 0.26 (50209 hom.)
• Consequence: TXNDC2 NM_032243.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.618
• Publications: 9 publications found

Genes affected

TXNDC2 (HGNC:16470): (thioredoxin domain containing 2) Enables thioredoxin-disulfide reductase activity. Predicted to be involved in cell differentiation and cellular oxidant detoxification. Predicted to act upstream of or within cellular response to reactive oxygen species and flagellated sperm motility. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 18-9886893-A-G is Benign according to our data. Variant chr18-9886893-A-G is described in ClinVar as Benign. ClinVar VariationId is 1225052.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.618 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032243.6. 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
	TXNDC2	NM_032243.6	MANE Select	c.213A>G	p.Ser71Ser	synonymous	Exon 2 of 2	NP_115619.4
	TXNDC2	NM_001098529.2		c.414A>G	p.Ser138Ser	synonymous	Exon 2 of 2	NP_001091999.1	A0A140VJY8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC2	ENST00000357775.6	TSL:1 MANE Select	c.213A>G	p.Ser71Ser	synonymous	Exon 2 of 2	ENSP00000350419.4	Q86VQ3-2
	TXNDC2	ENST00000306084.6	TSL:1	c.414A>G	p.Ser138Ser	synonymous	Exon 2 of 2	ENSP00000304908.6	Q86VQ3-1
	TXNDC2	ENST00000536353.2	TSL:5	c.213A>G	p.Ser71Ser	synonymous	Exon 2 of 3	ENSP00000437393.2	F5H6S7

Frequencies

GnomAD3 genomes AF: 0.245 AC: 36848 AN: 150292 Hom.: 4342 Cov.: 29

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.00194

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.250

GnomAD2 exomes AF: 0.226 AC: 56769 AN: 251018 AF XY: 0.231

Gnomad AFR exome AF: 0.267

Gnomad AMR exome AF: 0.132

Gnomad ASJ exome AF: 0.366

Gnomad EAS exome AF: 0.000707

Gnomad FIN exome AF: 0.244

Gnomad NFE exome AF: 0.271

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.258 AC: 376086 AN: 1460280 Hom.: 50209 Cov.: 102 AF XY: 0.257 AC XY: 186802 AN XY: 726460

African (AFR) AF: 0.271 AC: 8968 AN: 33032

American (AMR) AF: 0.141 AC: 6301 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 9438 AN: 26082

East Asian (EAS) AF: 0.000655 AC: 26 AN: 39686

South Asian (SAS) AF: 0.216 AC: 18622 AN: 86116

European-Finnish (FIN) AF: 0.247 AC: 13184 AN: 53412

Middle Eastern (MID) AF: 0.300 AC: 1728 AN: 5756

European-Non Finnish (NFE) AF: 0.272 AC: 302103 AN: 1111256

Other (OTH) AF: 0.261 AC: 15716 AN: 60310

GnomAD4 genome AF: 0.245 AC: 36859 AN: 150408 Hom.: 4343 Cov.: 29 AF XY: 0.239 AC XY: 17566 AN XY: 73508

African (AFR) AF: 0.259 AC: 10594 AN: 40830

American (AMR) AF: 0.188 AC: 2840 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1215 AN: 3438

East Asian (EAS) AF: 0.00195 AC: 10 AN: 5134

South Asian (SAS) AF: 0.194 AC: 922 AN: 4756

European-Finnish (FIN) AF: 0.239 AC: 2495 AN: 10422

Middle Eastern (MID) AF: 0.262 AC: 76 AN: 290

European-Non Finnish (NFE) AF: 0.266 AC: 17897 AN: 67408

Other (OTH) AF: 0.246 AC: 513 AN: 2082

Alfa AF: 0.262 Hom.: 4066

Asia WGS AF: 0.0940 AC: 331 AN: 3468

EpiCase AF: 0.278

EpiControl AF: 0.273

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.59
PhyloP100		-0.62
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: rs601874; hg19: chr18-9886890; COSMIC: COSV60156178;