chr16-11679695-C-T

Variant names:

• chr16-11679695-C-T
• rs1293111741
• NM_015914.7:c.2377G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015914.7(TXNDC11):​c.2377G>A​(p.Ala793Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TXNDC11 NM_015914.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.709
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06955513).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC11	NM_015914.7	MANE Select	c.2377G>A	p.Ala793Thr	missense	Exon 12 of 12	NP_056998.4
	TXNDC11	NM_001303447.2		c.2458G>A	p.Ala820Thr	missense	Exon 13 of 13	NP_001290376.1	Q6PKC3-1
	TXNDC11	NM_001324022.2		c.1735G>A	p.Ala579Thr	missense	Exon 11 of 11	NP_001310951.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC11	ENST00000283033.10	TSL:2 MANE Select	c.2377G>A	p.Ala793Thr	missense	Exon 12 of 12	ENSP00000283033.5	Q6PKC3-2
	TXNDC11	ENST00000356957.7	TSL:1	c.2458G>A	p.Ala820Thr	missense	Exon 13 of 13	ENSP00000349439.3	Q6PKC3-1
	TXNDC11	ENST00000907109.1		c.2578G>A	p.Ala860Thr	missense	Exon 14 of 14	ENSP00000577168.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	19
DANN	Benign	0.61
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.71
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.036
Sift	Benign	0.64	T
Sift4G	Benign	0.29	T
Polyphen		0.11	B
Vest4		0.072
MVP		0.33
MPC		0.089
ClinPred		0.17	T
GERP RS		5.6
Varity_R		0.068
gMVP		0.51

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: rs1293111741; hg19: chr16-11773551;