rs2274482

Variant names:

• chr9-110303694-A-C
• rs2274482
• ENST00000374510.8:c.336T>G

Your query was ambiguous. Multiple possible variants found:

• chr9-110303694-A-C
• chr9-110303694-A-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001003936.4(TXNDC8):​c.336T>G​(p.Asp112Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000264 in 1,597,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: TXNDC8 NM_001003936.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0760
• Publications: 3 publications found

Genes affected

TXNDC8 (HGNC:31454): (thioredoxin domain containing 8) Involved in spermatogenesis. Located in Golgi apparatus. Biomarker of male infertility. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000302400 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.036065787).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003936.4. 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
	TXNDC8	NM_001424031.1	MANE Select	c.322-111T>G		intron	N/A	NP_001410960.1	Q6A555-1
	TXNDC8	NM_001003936.4		c.336T>G	p.Asp112Glu	missense	Exon 6 of 6	NP_001003936.1	Q6A555-2
	TXNDC8	NM_001286946.2		c.276T>G	p.Asp92Glu	missense	Exon 5 of 5	NP_001273875.1	B7ZME0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC8	ENST00000374510.8	TSL:1	c.336T>G	p.Asp112Glu	missense	Exon 6 of 6	ENSP00000363634.4	Q6A555-2
	TXNDC8	ENST00000423740.7	TSL:1	c.276T>G	p.Asp92Glu	missense	Exon 5 of 5	ENSP00000408768.2	B7ZME0
	TXNDC8	ENST00000374511.8	TSL:5 MANE Select	c.322-111T>G		intron	N/A	ENSP00000363635.3	Q6A555-1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152260 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000757 AC: 18 AN: 237884 AF XY: 0.0000621

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000473

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.000170

GnomAD4 exome AF: 0.000279 AC: 403 AN: 1445212 Hom.: 0 Cov.: 29 AF XY: 0.000257 AC XY: 185 AN XY: 718714

African (AFR) AF: 0.000122 AC: 4 AN: 32796

American (AMR) AF: 0.00 AC: 0 AN: 44040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25714

East Asian (EAS) AF: 0.00 AC: 0 AN: 39246

South Asian (SAS) AF: 0.00 AC: 0 AN: 84764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4668

European-Non Finnish (NFE) AF: 0.000342 AC: 377 AN: 1101770

Other (OTH) AF: 0.000370 AC: 22 AN: 59468

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152260 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74386

African (AFR) AF: 0.00 AC: 0 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000458 Hom.: 0

Bravo AF: 0.000121

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000660 AC: 8

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	0.13
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.4
DANN	Uncertain	0.98
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.076
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.016
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.22	B
Vest4		0.054
MutPred		0.16		Gain of disorder (P = 0.1704)
MVP		0.068
MPC		0.015
ClinPred		0.058	T
GERP RS		1.1
gMVP		0.071
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2274482; hg19: chr9-113065974;