chr16-11679628-C-G

Variant names:

• chr16-11679628-C-G
• rs767623872
• NM_015914.7:c.2444G>C

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.2444G>C​(p.Ser815Thr) 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. 16/22 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. S815R) 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: 2.06
• 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=0.062681735).

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.2444G>C	p.Ser815Thr	missense	Exon 12 of 12	NP_056998.4
	TXNDC11	NM_001303447.2		c.2525G>C	p.Ser842Thr	missense	Exon 13 of 13	NP_001290376.1	Q6PKC3-1
	TXNDC11	NM_001324022.2		c.1802G>C	p.Ser601Thr	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.2444G>C	p.Ser815Thr	missense	Exon 12 of 12	ENSP00000283033.5	Q6PKC3-2
	TXNDC11	ENST00000356957.7	TSL:1	c.2525G>C	p.Ser842Thr	missense	Exon 13 of 13	ENSP00000349439.3	Q6PKC3-1
	TXNDC11	ENST00000907109.1		c.2645G>C	p.Ser882Thr	missense	Exon 14 of 14	ENSP00000577168.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.1
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.038
Sift	Benign	0.25	T
Sift4G	Benign	0.65	T
Polyphen		0.010	B
Vest4		0.11
MutPred		0.28		Loss of helix (P = 0.079)
MVP		0.34
MPC		0.058
ClinPred		0.14	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.24

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: rs767623872; hg19: chr16-11773484;