7-105542547-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1

The NM_021930.6(RINT1):​c.413C>T​(p.Ala138Val) variant causes a missense change. The variant allele was found at a frequency of 0.00078 in 1,614,134 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A138T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00062 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00080 ( 0 hom. )

Consequence

RINT1
NM_021930.6 missense

Scores

1
3
15

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.31
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.040397584).
BP6
Variant 7-105542547-C-T is Benign according to our data. Variant chr7-105542547-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 241408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-105542547-C-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000617 (94/152254) while in subpopulation NFE AF= 0.00103 (70/68018). AF 95% confidence interval is 0.000835. There are 1 homozygotes in gnomad4. There are 39 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RINT1NM_021930.6 linkc.413C>T p.Ala138Val missense_variant 4/15 ENST00000257700.7 NP_068749.3 Q6NUQ1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RINT1ENST00000257700.7 linkc.413C>T p.Ala138Val missense_variant 4/151 NM_021930.6 ENSP00000257700.2 Q6NUQ1

Frequencies

GnomAD3 genomes
AF:
0.000618
AC:
94
AN:
152136
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000362
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000459
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00103
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000465
AC:
117
AN:
251482
Hom.:
0
AF XY:
0.000441
AC XY:
60
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.000376
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.0000924
Gnomad NFE exome
AF:
0.000800
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000797
AC:
1165
AN:
1461880
Hom.:
0
Cov.:
31
AF XY:
0.000785
AC XY:
571
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.000313
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000267
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.000968
Gnomad4 OTH exome
AF:
0.000762
GnomAD4 genome
AF:
0.000617
AC:
94
AN:
152254
Hom.:
1
Cov.:
32
AF XY:
0.000524
AC XY:
39
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.000361
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00103
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000736
Hom.:
0
Bravo
AF:
0.000472
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.000428
AC:
52
EpiCase
AF:
0.000545
EpiControl
AF:
0.000652

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJul 02, 2020This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 23, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.058
T;.
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.15
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.86
D;D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.040
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
L;.
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.50
N;N
REVEL
Benign
0.094
Sift
Benign
0.70
T;T
Sift4G
Benign
0.31
T;D
Polyphen
0.23
B;.
Vest4
0.14
MVP
0.41
MPC
0.19
ClinPred
0.037
T
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.089
gMVP
0.34

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs150793856; hg19: chr7-105182994; COSMIC: COSV99994333; COSMIC: COSV99994333; API