rs3733897

Variant names:

• chr5-134887903-A-G
• rs3733897
• NM_024715.4:c.312A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024715.4(TXNDC15):​c.312A>G​(p.Lys104Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,614,102 control chromosomes in the GnomAD database, including 17,715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1341 hom., cov: 33)
  • Exomes 𝑓: 0.14 (16374 hom.)
• Consequence: TXNDC15 NM_024715.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.543
• Publications: 34 publications found

Genes affected

TXNDC15 (HGNC:20652): (thioredoxin domain containing 15) This gene encodes a member of the thioredoxin superfamily. Members of this family are characterized by a conserved active motif called the thioredoxin fold that catalyzes disulfide bond formation and isomerization. [provided by RefSeq, Apr 2017]

TXNDC15 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: STRONG Submitted by: ClinGen
• meckel syndrome 14

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Meckel syndrome

  Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 5-134887903-A-G is Benign according to our data. Variant chr5-134887903-A-G is described in ClinVar as Benign. ClinVar VariationId is 1559526.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024715.4. 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
	TXNDC15	NM_024715.4	MANE Select	c.312A>G	p.Lys104Lys	synonymous	Exon 2 of 5	NP_078991.3
	TXNDC15	NM_001350735.2		c.108A>G	p.Lys36Lys	synonymous	Exon 2 of 5	NP_001337664.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC15	ENST00000358387.9	TSL:1 MANE Select	c.312A>G	p.Lys104Lys	synonymous	Exon 2 of 5	ENSP00000351157.5	Q96J42-1
	TXNDC15	ENST00000507024.5	TSL:1	n.*130A>G		non_coding_transcript_exon	Exon 2 of 5	ENSP00000424716.1	D6RAV9
	TXNDC15	ENST00000507024.5	TSL:1	n.*130A>G		3_prime_UTR	Exon 2 of 5	ENSP00000424716.1	D6RAV9

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18581 AN: 152112 Hom.: 1336 Cov.: 33

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.112

GnomAD2 exomes AF: 0.151 AC: 37881 AN: 251418 AF XY: 0.152

Gnomad AFR exome AF: 0.0535

Gnomad AMR exome AF: 0.168

Gnomad ASJ exome AF: 0.0790

Gnomad EAS exome AF: 0.244

Gnomad FIN exome AF: 0.204

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.143 AC: 208423 AN: 1461872 Hom.: 16374 Cov.: 32 AF XY: 0.144 AC XY: 104528 AN XY: 727236

African (AFR) AF: 0.0507 AC: 1699 AN: 33480

American (AMR) AF: 0.168 AC: 7513 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0797 AC: 2083 AN: 26136

East Asian (EAS) AF: 0.323 AC: 12821 AN: 39698

South Asian (SAS) AF: 0.196 AC: 16900 AN: 86258

European-Finnish (FIN) AF: 0.206 AC: 11002 AN: 53418

Middle Eastern (MID) AF: 0.115 AC: 661 AN: 5768

European-Non Finnish (NFE) AF: 0.133 AC: 147350 AN: 1111996

Other (OTH) AF: 0.139 AC: 8394 AN: 60396

GnomAD4 genome AF: 0.122 AC: 18599 AN: 152230 Hom.: 1341 Cov.: 33 AF XY: 0.126 AC XY: 9408 AN XY: 74424

African (AFR) AF: 0.0549 AC: 2282 AN: 41560

American (AMR) AF: 0.154 AC: 2356 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0818 AC: 284 AN: 3472

East Asian (EAS) AF: 0.266 AC: 1374 AN: 5164

South Asian (SAS) AF: 0.196 AC: 947 AN: 4822

European-Finnish (FIN) AF: 0.197 AC: 2089 AN: 10588

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8873 AN: 68012

Other (OTH) AF: 0.112 AC: 237 AN: 2110

Alfa AF: 0.124 Hom.: 2361

Bravo AF: 0.116

Asia WGS AF: 0.224 AC: 776 AN: 3478

EpiCase AF: 0.124

EpiControl AF: 0.125

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	13
DANN	Benign	0.61
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.34		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3733897; hg19: chr5-134223593; COSMIC: COSV64379267; COSMIC: COSV64379267;