NM_015914.7:c.2266G>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015914.7(TXNDC11):​c.2266G>C​(p.Val756Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 1,612,060 control chromosomes in the GnomAD database, including 233,485 homozygotes. 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: 𝑓 0.51 (19976 hom., cov: 31)
  • Exomes 𝑓: 0.54 (213509 hom.)
• Consequence: TXNDC11 NM_015914.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• Publications: 32 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.9213159E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

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>C	p.Val756Leu	missense	Exon 12 of 12	NP_056998.4
	TXNDC11	NM_001303447.2		c.2347G>C	p.Val783Leu	missense	Exon 13 of 13	NP_001290376.1
	TXNDC11	NM_001324022.2		c.1624G>C	p.Val542Leu	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>C	p.Val756Leu	missense	Exon 12 of 12	ENSP00000283033.5
	TXNDC11	ENST00000356957.7	TSL:1	c.2347G>C	p.Val783Leu	missense	Exon 13 of 13	ENSP00000349439.3
	TXNDC11	ENST00000570917.5	TSL:5	n.476G>C		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76850 AN: 151738 Hom.: 19957 Cov.: 31

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.516

GnomAD2 exomes AF: 0.500 AC: 125615 AN: 250996 AF XY: 0.510

Gnomad AFR exome AF: 0.443

Gnomad AMR exome AF: 0.299

Gnomad ASJ exome AF: 0.697

Gnomad EAS exome AF: 0.420

Gnomad FIN exome AF: 0.534

Gnomad NFE exome AF: 0.558

Gnomad OTH exome AF: 0.523

GnomAD4 exome AF: 0.537 AC: 784283 AN: 1460204 Hom.: 213509 Cov.: 48 AF XY: 0.537 AC XY: 390218 AN XY: 726236

African (AFR) AF: 0.443 AC: 14809 AN: 33444

American (AMR) AF: 0.312 AC: 13959 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 18238 AN: 26118

East Asian (EAS) AF: 0.462 AC: 18323 AN: 39666

South Asian (SAS) AF: 0.504 AC: 43430 AN: 86228

European-Finnish (FIN) AF: 0.529 AC: 28259 AN: 53412

Middle Eastern (MID) AF: 0.616 AC: 3523 AN: 5718

European-Non Finnish (NFE) AF: 0.551 AC: 611684 AN: 1110578

Other (OTH) AF: 0.531 AC: 32058 AN: 60334

GnomAD4 genome AF: 0.506 AC: 76899 AN: 151856 Hom.: 19976 Cov.: 31 AF XY: 0.504 AC XY: 37443 AN XY: 74220

African (AFR) AF: 0.448 AC: 18556 AN: 41388

American (AMR) AF: 0.397 AC: 6065 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2373 AN: 3470

East Asian (EAS) AF: 0.423 AC: 2176 AN: 5148

South Asian (SAS) AF: 0.505 AC: 2431 AN: 4810

European-Finnish (FIN) AF: 0.538 AC: 5672 AN: 10540

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.556 AC: 37755 AN: 67924

Other (OTH) AF: 0.520 AC: 1099 AN: 2114

Alfa AF: 0.562 Hom.: 7896

Bravo AF: 0.490

TwinsUK AF: 0.544 AC: 2017

ALSPAC AF: 0.559 AC: 2153

ESP6500AA AF: 0.436 AC: 1914

ESP6500EA AF: 0.542 AC: 4661

ExAC AF: 0.507 AC: 61502

Asia WGS AF: 0.478 AC: 1662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.65
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.051	T
MetaRNN	Benign	0.000029	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.6	N
PhyloP100		1.5
PrimateAI	Benign	0.31	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.035
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.042
MPC		0.059
ClinPred		0.0016	T
GERP RS		3.6
Varity_R		0.042
gMVP		0.46
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV51599227; COSMIC: COSV51599227;