chr5-134893571-CCAGTTTGGCCCCTCA-C

Variant names:

• chr5-134893571-CCAGTTTGGCCCCTCA-C
• rs886039791
• NM_024715.4:c.673_687delAGTTTGGCCCCTCAC

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM4 PP3 PP5_Moderate

The NM_024715.4(TXNDC15):​c.673_687delAGTTTGGCCCCTCAC​(p.Ser225_His229del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TXNDC15 NM_024715.4 conservative_inframe_deletion
• Clinical Significance: Pathogenic criteria provided, single submitter P:3
• Conservation: PhyloP100: 7.54
• Publications: 3 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: Uncertain_significance. The variant received 5 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_024715.4.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 5-134893571-CCAGTTTGGCCCCTCA-C is Pathogenic according to our data. Variant chr5-134893571-CCAGTTTGGCCCCTCA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 266074.Status of the report is criteria_provided_single_submitter, 1 stars.

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.673_687delAGTTTGGCCCCTCAC	p.Ser225_His229del	conservative_inframe_deletion	Exon 3 of 5	NP_078991.3
	TXNDC15	NM_001350735.2		c.469_483delAGTTTGGCCCCTCAC	p.Ser157_His161del	conservative_inframe_deletion	Exon 3 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.673_687delAGTTTGGCCCCTCAC	p.Ser225_His229del	conservative_inframe_deletion	Exon 3 of 5	ENSP00000351157.5	Q96J42-1
	TXNDC15	ENST00000507024.5	TSL:1	n.*491_*505delAGTTTGGCCCCTCAC		non_coding_transcript_exon	Exon 3 of 5	ENSP00000424716.1	D6RAV9
	TXNDC15	ENST00000511070.5	TSL:1	n.*50_*64delAGTTTGGCCCCTCAC		non_coding_transcript_exon	Exon 2 of 4	ENSP00000423609.1	D6R962

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
2	-	-	Meckel syndrome 14 (2)
1	-	-	Meckel-Gruber syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.5
Mutation Taster		=1/199	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs886039791; hg19: chr5-134229261;