NM_024715.4:c.317G>T

Variant names:

• chr5-134887908-G-T
• NM_024715.4:c.317G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024715.4(TXNDC15):​c.317G>T​(p.Ser106Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 6.8e-7 (0 hom.)
• Consequence: TXNDC15 NM_024715.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.693

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.098605424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNDC15	NM_024715.4	c.317G>T	p.Ser106Ile	missense_variant	Exon 2 of 5	ENST00000358387.9	NP_078991.3
TXNDC15	NM_001350735.2	c.113G>T	p.Ser38Ile	missense_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.317G>T	p.Ser106Ile	missense_variant	Exon 2 of 5	1	NM_024715.4	ENSP00000351157.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727242

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.019	T;T;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.099	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.72	N;D;N
REVEL	Benign	0.035
Sift	Benign	0.088	T;T;T
Sift4G	Benign	0.11	T;D;T
Polyphen		0.14	B;.;.
Vest4		0.21
MutPred		0.27		Loss of disorder (P = 0.0195);.;.;
MVP		0.41
MPC		0.23
ClinPred		0.14	T
GERP RS		3.7
Varity_R		0.065
gMVP		0.43

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-134223598;