rs756023205

Variant names:

• chr5-134887684-GC-G
• rs756023205
• NM_024715.4:c.104-10delC

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The NM_024715.4(TXNDC15):​c.104-10delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,554,846 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: TXNDC15 NM_024715.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.449
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 5-134887684-GC-G is Benign according to our data. Variant chr5-134887684-GC-G is described in ClinVar as Benign. ClinVar VariationId is 2084183.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000407 (62/152188) while in subpopulation AMR AF = 0.0038 (58/15280). AF 95% confidence interval is 0.00301. There are 0 homozygotes in GnomAd4. There are 34 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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.104-10delC		intron	N/A	NP_078991.3
	TXNDC15	NM_001350735.2		c.-101-10delC		intron	N/A	NP_001337664.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC15	ENST00000358387.9	TSL:1 MANE Select	c.104-10delC		intron	N/A	ENSP00000351157.5	Q96J42-1
	TXNDC15	ENST00000507024.5	TSL:1	n.57-10delC		intron	N/A	ENSP00000424716.1	D6RAV9
	TXNDC15	ENST00000511070.5	TSL:1	n.104-5807delC		intron	N/A	ENSP00000423609.1	D6R962

Frequencies

GnomAD3 genomes AF: 0.000407 AC: 62 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

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: 0.0000294

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000297 AC: 63 AN: 212350 AF XY: 0.000176

Gnomad AFR exome AF: 0.0000637

Gnomad AMR exome AF: 0.00199

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000502

Gnomad OTH exome AF: 0.000397

GnomAD4 exome AF: 0.000103 AC: 145 AN: 1402658 Hom.: 0 Cov.: 30 AF XY: 0.000101 AC XY: 70 AN XY: 690132

African (AFR) AF: 0.0000627 AC: 2 AN: 31876

American (AMR) AF: 0.00199 AC: 73 AN: 36768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22506

East Asian (EAS) AF: 0.00 AC: 0 AN: 38962

South Asian (SAS) AF: 0.00 AC: 0 AN: 76772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5486

European-Non Finnish (NFE) AF: 0.0000555 AC: 60 AN: 1081024

Other (OTH) AF: 0.000173 AC: 10 AN: 57804

GnomAD4 genome AF: 0.000407 AC: 62 AN: 152188 Hom.: 0 Cov.: 33 AF XY: 0.000457 AC XY: 34 AN XY: 74362

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00380 AC: 58 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000487

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
PhyloP100		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs756023205; hg19: chr5-134223374;