rs111331197

Variant names:

• chr6-7883235-C-G
• rs111331197
• NM_030810.5:c.1208G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-7883235-C-G
• chr6-7883235-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_030810.5(TXNDC5):​c.1208G>C​(p.Arg403Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TXNDC5 NM_030810.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98

Genes affected

TXNDC5 (HGNC:21073): (thioredoxin domain containing 5) This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal endoplasmic reticulum (ER)-signal sequence, three catalytically active thioredoxin domains and a C-terminal ER-retention sequence. Its expression is induced by hypoxia and its role may be to protect hypoxic cells from apoptosis. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring upstream BLOC1S5 gene. [provided by RefSeq, Dec 2016]

BLOC1S5-TXNDC5 (HGNC:42001): (BLOC1S5-TXNDC5 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring MUTED (muted homolog) and TXNDC5 (thioredoxin domain containing 5) genes on chromosome 6. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.825

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNDC5	NM_030810.5	c.1208G>C	p.Arg403Pro	missense_variant	Exon 10 of 10	ENST00000379757.9	NP_110437.2
TXNDC5	NM_001145549.4	c.884G>C	p.Arg295Pro	missense_variant	Exon 10 of 10		NP_001139021.1
BLOC1S5-TXNDC5	NR_037616.1	n.1367G>C		non_coding_transcript_exon_variant	Exon 13 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNDC5	ENST00000379757.9	c.1208G>C	p.Arg403Pro	missense_variant	Exon 10 of 10	1	NM_030810.5	ENSP00000369081.4
BLOC1S5-TXNDC5	ENST00000439343.2	n.*906G>C		non_coding_transcript_exon_variant	Exon 13 of 13	2		ENSP00000454697.1
BLOC1S5-TXNDC5	ENST00000439343.2	n.*906G>C		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000454697.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.87	L;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0030	D;D
Sift4G	Benign	0.096	T;D
Polyphen		1.0	D;.
Vest4		0.61
MutPred		0.76		Loss of MoRF binding (P = 0.004);.;
MVP		0.36
MPC		0.69
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.97
gMVP		0.98

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs111331197; hg19: chr6-7883468;