NM_024715.4:c.203C>G

Variant names:

• chr5-134887794-C-G
• rs764634537
• NM_024715.4:c.203C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024715.4(TXNDC15):​c.203C>G​(p.Pro68Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TXNDC15 NM_024715.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.766

Genes affected

TXNDC15 (HGNC:20652): (thioredoxin domain containing 15) This gene encodes a member of the thioredoxin superfamily. Members of this family are characterized by a conserved active motif called the thioredoxin fold that catalyzes disulfide bond formation and isomerization. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05937314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNDC15	NM_024715.4	c.203C>G	p.Pro68Arg	missense_variant	Exon 2 of 5	ENST00000358387.9	NP_078991.3
TXNDC15	NM_001350735.2	c.-2C>G		5_prime_UTR_variant	Exon 2 of 5		NP_001337664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNDC15	ENST00000358387.9	c.203C>G	p.Pro68Arg	missense_variant	Exon 2 of 5	1	NM_024715.4	ENSP00000351157.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251262 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135808

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 SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.9
DANN	Benign	0.74
DEOGEN2	Benign	0.013	T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.36	T;T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.059	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N;N;D
REVEL	Benign	0.039
Sift	Benign	0.036	D;T;T
Sift4G	Benign	0.090	T;T;T
Polyphen		0.0040	B;.;.
Vest4		0.067
MutPred		0.19		Loss of helix (P = 0.028);.;.;
MVP		0.092
MPC		0.19
ClinPred		0.046	T
GERP RS		-5.8
Varity_R		0.034
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs764634537; hg19: chr5-134223484;