rs878855071

Variant names:

• chr7-105551565-ATCAGTT-TCA
• rs878855071
• NM_021930.6:c.1334-5_1335delATCAGTTinsTCA

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_021930.6(RINT1):​c.1334-5_1335delATCAGTTinsTCA​(p.Phe445fs) variant causes a frameshift, splice acceptor, splice region, synonymous, intron 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. F445F) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RINT1 NM_021930.6 frameshift, splice_acceptor, splice_region, synonymous, intron
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 9.83
• Publications: 0 publications found

Genes affected

RINT1 (HGNC:21876): (RAD50 interactor 1) This gene encodes a protein first identified for its ability to interact with the RAD50 double strand break repair protein, with the resulting interaction implicated in the regulation of cell cycle progression and telomere length. The encoded protein may also play a role in trafficking of cellular cargo from the endosome to the trans-Golgi network. Mutations in this gene may be associated with breast cancer in human patients. [provided by RefSeq, Oct 2016]

RINT1 Gene-Disease associations (from GenCC):

• infantile liver failure syndrome 3

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• infantile liver failure syndrome 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• breast cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• familial ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021930.6. 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
	RINT1	NM_021930.6	MANE Select	c.1334-5_1335delATCAGTTinsTCA	p.Phe445fs	frameshift splice_acceptor splice_region synonymous intron	Exon 10 of 15	NP_068749.3
	RINT1	NM_001346599.2		c.1100-5_1101delATCAGTTinsTCA	p.Phe367fs	frameshift splice_acceptor splice_region synonymous intron	Exon 10 of 15	NP_001333528.1
	RINT1	NM_001346601.2		c.410-5_411delATCAGTTinsTCA	p.Phe137fs	frameshift splice_acceptor splice_region synonymous intron	Exon 10 of 15	NP_001333530.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RINT1	ENST00000257700.7	TSL:1 MANE Select	c.1334-5_1335delATCAGTTinsTCA	p.Phe445fs	frameshift splice_acceptor splice_region synonymous intron	Exon 10 of 15	ENSP00000257700.2	Q6NUQ1
	RINT1	ENST00000967558.1		c.1463-5_1464delATCAGTTinsTCA	p.Phe488fs	frameshift splice_acceptor splice_region synonymous intron	Exon 10 of 15	ENSP00000637617.1
	RINT1	ENST00000899074.1		c.1334-5_1335delATCAGTTinsTCA	p.Phe445fs	frameshift splice_acceptor splice_region synonymous intron	Exon 10 of 16	ENSP00000569133.1

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 as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.8

Splicing

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

Other links and lift over

dbSNP: rs878855071; hg19: chr7-105192012;