chr17-6641191-G-A

Variant names:

• chr17-6641191-G-A
• rs775745043
• NM_032731.4:c.109G>A

Variant summary

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

The NM_032731.4(TXNDC17):​c.109G>A​(p.Ala37Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A37S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TXNDC17 NM_032731.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.62
• Publications: 0 publications found

Genes affected

TXNDC17 (HGNC:28218): (thioredoxin domain containing 17) Enables peroxidase activity and protein-disulfide reductase (NAD(P)) activity. Involved in tumor necrosis factor-mediated signaling pathway. Located in cytosol. [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=0.10983673).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032731.4. 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
	TXNDC17	NM_032731.4	MANE Select	c.109G>A	p.Ala37Thr	missense	Exon 1 of 4	NP_116120.1	A0A140VJY7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC17	ENST00000250101.10	TSL:1 MANE Select	c.109G>A	p.Ala37Thr	missense	Exon 1 of 4	ENSP00000250101.5	Q9BRA2
	TXNDC17	ENST00000939770.1		c.109G>A	p.Ala37Thr	missense	Exon 1 of 4	ENSP00000609829.1
	TXNDC17	ENST00000939769.1		c.109G>A	p.Ala37Thr	missense	Exon 1 of 4	ENSP00000609828.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.074
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	N
PhyloP100		3.6
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.010
Sift	Benign	0.27	T
Sift4G	Benign	0.50	T
Polyphen		0.069	B
Vest4		0.15
MutPred		0.27		Loss of catalytic residue at A37 (P = 0.0742)
MVP		0.42
MPC		0.16
ClinPred		0.30	T
GERP RS		2.1
PromoterAI		-0.046	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.13
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs775745043; hg19: chr17-6544511;