16-11679695-C-A

Variant names:

• chr16-11679695-C-A
• rs1293111741
• NM_015914.7:c.2377G>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.2377G>T​(p.Ala793Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A793T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TXNDC11 NM_015914.7 missense
• Clinical Significance: Not reported in ClinVar
• 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: 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=0.067892194).

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>T	p.Ala793Ser	missense	Exon 12 of 12	NP_056998.4
	TXNDC11	NM_001303447.2		c.2458G>T	p.Ala820Ser	missense	Exon 13 of 13	NP_001290376.1	Q6PKC3-1
	TXNDC11	NM_001324022.2		c.1735G>T	p.Ala579Ser	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>T	p.Ala793Ser	missense	Exon 12 of 12	ENSP00000283033.5	Q6PKC3-2
	TXNDC11	ENST00000356957.7	TSL:1	c.2458G>T	p.Ala820Ser	missense	Exon 13 of 13	ENSP00000349439.3	Q6PKC3-1
	TXNDC11	ENST00000907109.1		c.2578G>T	p.Ala860Ser	missense	Exon 14 of 14	ENSP00000577168.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	19
DANN	Benign	0.64
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.71
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.050
Sift	Benign	0.82	T
Sift4G	Benign	0.33	T
Polyphen		0.26	B
Vest4		0.14
MutPred		0.21		Gain of disorder (P = 0.0963)
MVP		0.34
MPC		0.11
ClinPred		0.18	T
GERP RS		5.6
Varity_R		0.077
gMVP		0.44

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;