chr16-11679498-C-G

Variant names:

• chr16-11679498-C-G
• rs765045815
• NM_015914.7:c.2574G>C

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.2574G>C​(p.Gln858His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TXNDC11 NM_015914.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.223
• 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=0.08821297).

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.2574G>C	p.Gln858His	missense	Exon 12 of 12	NP_056998.4
	TXNDC11	NM_001303447.2		c.2655G>C	p.Gln885His	missense	Exon 13 of 13	NP_001290376.1	Q6PKC3-1
	TXNDC11	NM_001324022.2		c.1932G>C	p.Gln644His	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.2574G>C	p.Gln858His	missense	Exon 12 of 12	ENSP00000283033.5	Q6PKC3-2
	TXNDC11	ENST00000356957.7	TSL:1	c.2655G>C	p.Gln885His	missense	Exon 13 of 13	ENSP00000349439.3	Q6PKC3-1
	TXNDC11	ENST00000907109.1		c.2775G>C	p.Gln925His	missense	Exon 14 of 14	ENSP00000577168.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152250 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 250404 AF XY: 0.00

Gnomad AFR exome AF: 0.000249

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 1461180 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726952

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 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: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52720

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152250 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74390

African (AFR) AF: 0.0000723 AC: 3 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000165 AC: 2

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	0.23
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.94
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.22
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.012
Sift	Benign	0.20	T
Sift4G	Benign	0.21	T
Polyphen		0.091	B
Vest4		0.21
MutPred		0.27		Loss of helix (P = 0.0237)
MVP		0.35
MPC		0.069
ClinPred		0.035	T
GERP RS		1.5
Varity_R		0.051
gMVP		0.19
Mutation Taster		=92/8	polymorphism

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: rs765045815; hg19: chr16-11773354;