rs111331197

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-7883235-C-T
• chr6-7883235-C-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_030810.5(TXNDC5):​c.1208G>A​(p.Arg403Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00905 in 1,614,122 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0068 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0093 (69 hom.)
• Consequence: TXNDC5 NM_030810.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.98
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008690864).
• BP6: Variant 6-7883235-C-T is Benign according to our data. Variant chr6-7883235-C-T is described in ClinVar as Benign. ClinVar VariationId is 780037.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030810.5. 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
	TXNDC5	NM_030810.5	MANE Select	c.1208G>A	p.Arg403Gln	missense	Exon 10 of 10	NP_110437.2
	TXNDC5	NM_001145549.4		c.884G>A	p.Arg295Gln	missense	Exon 10 of 10	NP_001139021.1	Q8NBS9-2
	BLOC1S5-TXNDC5	NR_037616.1		n.1367G>A		non_coding_transcript_exon	Exon 13 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC5	ENST00000379757.9	TSL:1 MANE Select	c.1208G>A	p.Arg403Gln	missense	Exon 10 of 10	ENSP00000369081.4	Q8NBS9-1
	TXNDC5	ENST00000473453.2	TSL:1	c.884G>A	p.Arg295Gln	missense	Exon 10 of 10	ENSP00000420784.1	Q8NBS9-2
	BLOC1S5-TXNDC5	ENST00000439343.2	TSL:2	n.*906G>A		non_coding_transcript_exon	Exon 13 of 13	ENSP00000454697.1	H3BN57

Frequencies

GnomAD3 genomes AF: 0.00678 AC: 1032 AN: 152126 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00661

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00510

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.00863

GnomAD2 exomes AF: 0.00700 AC: 1760 AN: 251260 AF XY: 0.00742

Gnomad AFR exome AF: 0.000984

Gnomad AMR exome AF: 0.00665

Gnomad ASJ exome AF: 0.00685

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00587

Gnomad NFE exome AF: 0.0104

Gnomad OTH exome AF: 0.00733

GnomAD4 exome AF: 0.00928 AC: 13571 AN: 1461878 Hom.: 69 Cov.: 30 AF XY: 0.00898 AC XY: 6534 AN XY: 727236

African (AFR) AF: 0.00128 AC: 43 AN: 33480

American (AMR) AF: 0.00678 AC: 303 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00685 AC: 179 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00322 AC: 278 AN: 86256

European-Finnish (FIN) AF: 0.00505 AC: 270 AN: 53414

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5768

European-Non Finnish (NFE) AF: 0.0107 AC: 11938 AN: 1112006

Other (OTH) AF: 0.00901 AC: 544 AN: 60396

GnomAD4 genome AF: 0.00678 AC: 1032 AN: 152244 Hom.: 4 Cov.: 32 AF XY: 0.00636 AC XY: 473 AN XY: 74420

African (AFR) AF: 0.00197 AC: 82 AN: 41550

American (AMR) AF: 0.00660 AC: 101 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4820

European-Finnish (FIN) AF: 0.00510 AC: 54 AN: 10598

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0109 AC: 739 AN: 68010

Other (OTH) AF: 0.00854 AC: 18 AN: 2108

Alfa AF: 0.00900 Hom.: 14

Bravo AF: 0.00689

TwinsUK AF: 0.0102 AC: 38

ALSPAC AF: 0.00908 AC: 35

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.0127 AC: 109

ExAC AF: 0.00721 AC: 875

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00965

EpiControl AF: 0.00942

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.0087	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.84	L
PhyloP100		4.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.20
Sift	Benign	0.068	T
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.24
MVP		0.35
MPC		0.59
ClinPred		0.036	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.88
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs111331197; hg19: chr6-7883468; COSMIC: COSV51665537; COSMIC: COSV51665537;