chr5-134893571-CCAGTTTGGCCCCTCA-C

Variant names:

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

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 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. 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

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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 id is 266074.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNDC15	NM_024715.4	c.673_687delAGTTTGGCCCCTCAC	p.Ser225_His229del	conservative_inframe_deletion	Exon 3 of 5	ENST00000358387.9	NP_078991.3
TXNDC15	NM_001350735.2	c.469_483delAGTTTGGCCCCTCAC	p.Ser157_His161del	conservative_inframe_deletion	Exon 3 of 5		NP_001337664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNDC15	ENST00000358387.9	c.673_687delAGTTTGGCCCCTCAC	p.Ser225_His229del	conservative_inframe_deletion	Exon 3 of 5	1	NM_024715.4	ENSP00000351157.5

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

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, single submitter

Submissions by phenotype

Meckel syndrome 14 Pathogenic:2

Sep 22, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 13, 2022

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Meckel-Gruber syndrome Pathogenic:1

-

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: research

Loss of function, autozygosity mapping, segregation, gene independently mutated in three families with Meckel-Gruber syndrome, experimental evidence linking TXNDC15 to ciliogenesis -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs886039791; hg19: chr5-134229261;