14-52470087-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_020784.3(TXNDC16):c.1568T>C(p.Leu523Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TXNDC16 NM_020784.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.91

Genes affected

TXNDC16 (HGNC:19965): (thioredoxin domain containing 16) Located in endoplasmic reticulum lumen. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058053344).
• BP6: Variant 14-52470087-A-G is Benign according to our data. Variant chr14-52470087-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3185163.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNDC16	NM_020784.3	c.1568T>C	p.Leu523Ser	missense_variant	16/21	ENST00000281741.9
TXNDC16	NM_001160047.2	c.1553T>C	p.Leu518Ser	missense_variant	16/21
TXNDC16	XR_007064037.1	n.1939T>C		non_coding_transcript_exon_variant	16/19
TXNDC16	XR_007064038.1	n.1939T>C		non_coding_transcript_exon_variant	16/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNDC16	ENST00000281741.9	c.1568T>C	p.Leu523Ser	missense_variant	16/21	1	NM_020784.3	P1
TXNDC16	ENST00000555312.1	c.251T>C	p.Leu84Ser	missense_variant, NMD_transcript_variant	2/5	5
TXNDC16	ENST00000554399.1	n.208-29363T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	5.2
Dann	Benign	0.17
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.0055	N
LIST_S2	Benign	0.098	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.5	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.098
Sift	Benign	0.92	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.39		Gain of disorder (P = 0.0361);
MVP		0.24
MPC		0.022
ClinPred		0.030	T
GERP RS		4.3
Varity_R		0.017
gMVP		0.29

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-52936805;