chr16-11679806-C-T

Position:

• chr16-11679806-C-T

Variant summary

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

The NM_015914.7(TXNDC11):​c.2266G>A​(p.Val756Ile) 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 1,460,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TXNDC11 NM_015914.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

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

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=0.05825162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNDC11	NM_015914.7	c.2266G>A	p.Val756Ile	missense_variant	12/12	ENST00000283033.10	NP_056998.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNDC11	ENST00000283033.10	c.2266G>A	p.Val756Ile	missense_variant	12/12	2	NM_015914.7	ENSP00000283033	P2
TXNDC11	ENST00000356957.7	c.2347G>A	p.Val783Ile	missense_variant	13/13	1		ENSP00000349439	A2
TXNDC11	ENST00000570917.5	n.476G>A		non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 250996 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135730

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

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: 1460882 Hom.: 0 Cov.: 48 AF XY: 0.00000275 AC XY: 2 AN XY: 726546

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.023	.;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.16	T;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	.;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.33	N;N
REVEL	Benign	0.042
Sift	Benign	0.057	T;D
Sift4G	Benign	0.22	T;T
Polyphen		0.014	B;B
Vest4		0.093
MutPred		0.45		.;Gain of ubiquitination at K778 (P = 0.0804);
MVP		0.17
MPC		0.051
ClinPred		0.20	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.048
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: rs3190321; hg19: chr16-11773662; COSMIC: COSV51599597; COSMIC: COSV51599597;