NM_006984.5:c.*11T>G

Variant names:

• chr13-95578025-T-G
• rs1325774
• NM_006984.5:c.*11T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006984.5(CLDN10):​c.*11T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,511,044 control chromosomes in the GnomAD database, including 82,957 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (7853 hom., cov: 32)
  • Exomes 𝑓: 0.33 (75104 hom.)
• Consequence: CLDN10 NM_006984.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0630
• Publications: 16 publications found

Genes affected

CLDN10 (HGNC:2033): (claudin 10) This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets, and also play critical roles in maintaining cell polarity and signal transductions. The expression level of this gene is associated with recurrence of primary hepatocellular carcinoma. Six alternatively spliced transcript variants encoding different isoforms have been reported, but the transcript sequences of some variants are not determined.[provided by RefSeq, Jun 2010]

DZIP1 (HGNC:20908): (DAZ interacting zinc finger protein 1) Predicted to enable metal ion binding activity. Involved in cilium assembly; germ cell development; and spermatogenesis. Located in cytosol; microtubule organizing center; and nucleoplasm. Colocalizes with centriole. Implicated in mitral valve prolapse and spermatogenic failure 47. [provided by Alliance of Genome Resources, Apr 2022]

DZIP1 Gene-Disease associations (from GenCC):

• spermatogenic failure 47

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 13-95578025-T-G is Benign according to our data. Variant chr13-95578025-T-G is described in ClinVar as Benign. ClinVar VariationId is 1271447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN10	NM_006984.5	c.*11T>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000299339.3	NP_008915.1
DZIP1	NM_198968.4	c.*4209A>C		downstream_gene_variant		ENST00000376829.7	NP_945319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN10	ENST00000299339.3	c.*11T>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_006984.5	ENSP00000299339.2
DZIP1	ENST00000376829.7	c.*4209A>C		downstream_gene_variant		1	NM_198968.4	ENSP00000366025.2

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48058 AN: 151998 Hom.: 7858 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.306

GnomAD2 exomes AF: 0.297 AC: 71238 AN: 239476 AF XY: 0.303

Gnomad AFR exome AF: 0.312

Gnomad AMR exome AF: 0.166

Gnomad ASJ exome AF: 0.285

Gnomad EAS exome AF: 0.143

Gnomad FIN exome AF: 0.375

Gnomad NFE exome AF: 0.346

Gnomad OTH exome AF: 0.316

GnomAD4 exome AF: 0.330 AC: 447963 AN: 1358926 Hom.: 75104 Cov.: 19 AF XY: 0.329 AC XY: 224361 AN XY: 681250

African (AFR) AF: 0.315 AC: 9806 AN: 31150

American (AMR) AF: 0.172 AC: 7435 AN: 43332

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 7374 AN: 25290

East Asian (EAS) AF: 0.140 AC: 5456 AN: 38984

South Asian (SAS) AF: 0.297 AC: 24603 AN: 82770

European-Finnish (FIN) AF: 0.371 AC: 19676 AN: 53028

Middle Eastern (MID) AF: 0.319 AC: 1775 AN: 5556

European-Non Finnish (NFE) AF: 0.346 AC: 353717 AN: 1021926

Other (OTH) AF: 0.319 AC: 18121 AN: 56890

GnomAD4 genome AF: 0.316 AC: 48057 AN: 152118 Hom.: 7853 Cov.: 32 AF XY: 0.314 AC XY: 23375 AN XY: 74374

African (AFR) AF: 0.312 AC: 12948 AN: 41490

American (AMR) AF: 0.248 AC: 3792 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1036 AN: 3470

East Asian (EAS) AF: 0.149 AC: 774 AN: 5186

South Asian (SAS) AF: 0.279 AC: 1343 AN: 4820

European-Finnish (FIN) AF: 0.391 AC: 4134 AN: 10572

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22964 AN: 67970

Other (OTH) AF: 0.302 AC: 637 AN: 2112

Alfa AF: 0.326 Hom.: 31724

Bravo AF: 0.303

Asia WGS AF: 0.225 AC: 784 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.2
DANN	Benign	0.74
PhyloP100		-0.063
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1325774; hg19: chr13-96230279; COSMIC: COSV54824421; COSMIC: COSV54824421;