rs9912315

Variant names:

• chr17-7260487-C-A
• rs9912315
• NM_001307.6:c.523G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-7260487-C-A
• chr17-7260487-C-G
• chr17-7260487-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001185023.2(CLDN7):​c.438G>T​(p.Ter146Tyrext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CLDN7 NM_001185023.2 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411

Genes affected

CLDN7 (HGNC:2049): (claudin 7) 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. Differential expression of this gene has been observed in different types of malignancies, including breast cancer, ovarian cancer, hepatocellular carcinomas, urinary tumors, prostate cancer, lung cancer, head and neck cancers, thyroid carcinomas, etc.. Alternatively spliced transcript variants encoding different isoforms have been found.[provided by RefSeq, May 2010]

ENSG00000262302 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_001185023.2 Downstream stopcodon found after 44 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN7	NM_001307.6	c.523G>T	p.Val175Phe	missense_variant	Exon 4 of 4	ENST00000360325.11	NP_001298.3
CLDN7	NM_001185023.2	c.438G>T	p.Ter146Tyrext*?	stop_lost	Exon 3 of 3		NP_001171952.1
CLDN7	NM_001185022.2	c.523G>T	p.Val175Phe	missense_variant	Exon 5 of 5		NP_001171951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN7	ENST00000360325.11	c.523G>T	p.Val175Phe	missense_variant	Exon 4 of 4	1	NM_001307.6	ENSP00000353475.7
ENSG00000262302	ENST00000577138.1	n.223+1334G>T		intron_variant	Intron 1 of 3	3		ENSP00000460571.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000317 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	9.6
DANN	Benign	0.85
DEOGEN2	Uncertain	0.50	T;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.24	N
LIST_S2	Uncertain	0.92	.;D;D
MetaRNN	Uncertain	0.63	D;D;D
MetaSVM	Benign	-0.87	T
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.4	N;N;.
REVEL	Uncertain	0.44
Sift	Benign	0.12	T;T;.
Sift4G	Benign	0.14	T;T;.
Polyphen		0.43	B;B;.
Vest4		0.25
MutPred		0.76		Loss of stability (P = 0.0591);Loss of stability (P = 0.0591);.;
MVP		0.89
MPC		0.62
ClinPred		0.22	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9912315; hg19: chr17-7163806;