rs1790066829

Variant names:

• chr7-105532346-C-G
• rs1790066829
• NM_021930.6:c.31C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-105532346-C-G
• chr7-105532346-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021930.6(RINT1):​c.31C>G​(p.Pro11Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P11S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RINT1 NM_021930.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324
• 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: Labcorp Genetics (formerly Invitae), G2P, 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
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000295934 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.115502924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RINT1	NM_021930.6	c.31C>G	p.Pro11Ala	missense_variant	Exon 1 of 15	ENST00000257700.7	NP_068749.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RINT1	ENST00000257700.7	c.31C>G	p.Pro11Ala	missense_variant	Exon 1 of 15	1	NM_021930.6	ENSP00000257700.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1448200 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 719660

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000602 AC: 2 AN: 33250

American (AMR) AF: 0.00 AC: 0 AN: 43336

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25822

East Asian (EAS) AF: 0.00 AC: 0 AN: 39134

South Asian (SAS) AF: 0.00 AC: 0 AN: 84144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49674

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107238

Other (OTH) AF: 0.00 AC: 0 AN: 59874

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.029673), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.6
DANN	Benign	0.81
DEOGEN2	Benign	0.070	T;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.
PhyloP100		0.32
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.60	N;N
REVEL	Benign	0.033
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.0010	B;.
Vest4		0.23
MutPred		0.27		Gain of catalytic residue at P11 (P = 0.0642);Gain of catalytic residue at P11 (P = 0.0642);
MVP		0.35
MPC		0.18
ClinPred		0.45	T
GERP RS		2.0
PromoterAI		-0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.9
Varity_R		0.13
gMVP		0.20
Mutation Taster		=98/2	polymorphism

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: rs1790066829; hg19: chr7-105172793;