rs3190321

Variant names:

• chr16-11679806-C-A
• rs3190321
• NM_015914.7:c.2266G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-11679806-C-A
• chr16-11679806-C-G
• chr16-11679806-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015914.7(TXNDC11):​c.2266G>T​(p.Val756Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TXNDC11 NM_015914.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• Publications: 0 publications found

Genes affected

TXNDC11 (HGNC:28030): (thioredoxin domain containing 11) Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060945928).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015914.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC11	NM_015914.7	MANE Select	c.2266G>T	p.Val756Phe	missense	Exon 12 of 12	NP_056998.4
	TXNDC11	NM_001303447.2		c.2347G>T	p.Val783Phe	missense	Exon 13 of 13	NP_001290376.1
	TXNDC11	NM_001324022.2		c.1624G>T	p.Val542Phe	missense	Exon 11 of 11	NP_001310951.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC11	ENST00000283033.10	TSL:2 MANE Select	c.2266G>T	p.Val756Phe	missense	Exon 12 of 12	ENSP00000283033.5
	TXNDC11	ENST00000356957.7	TSL:1	c.2347G>T	p.Val783Phe	missense	Exon 13 of 13	ENSP00000349439.3
	TXNDC11	ENST00000570917.5	TSL:5	n.476G>T		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460882 Hom.: 0 Cov.: 48 AF XY: 0.00000138 AC XY: 1 AN XY: 726546

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111186

Other (OTH) AF: 0.00 AC: 0 AN: 60352

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.84	N
PhyloP100		1.5
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.069
Sift	Benign	0.17	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.40		Loss of ubiquitination at K778 (P = 0.1079)
MVP		0.28
MPC		0.077
ClinPred		0.53	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.61
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs3190321; hg19: chr16-11773662;