7-105565281-T-G

Variant names:

• chr7-105565281-T-G
• rs763828038
• NM_021930.6:c.1891T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021930.6(RINT1):​c.1891T>G​(p.Leu631Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000349 in 1,432,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L631F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: RINT1 NM_021930.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.27
• Publications: 2 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]

EFCAB10 (HGNC:34531): (EF-hand calcium binding domain 10) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3380736).

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.1891T>G	p.Leu631Val	missense	Exon 13 of 15	NP_068749.3
	EFCAB10	NM_001355526.2	MANE Select	c.*166A>C		3_prime_UTR	Exon 5 of 5	NP_001342455.1	A6NFE3
	RINT1	NM_001346599.2		c.1657T>G	p.Leu553Val	missense	Exon 13 of 15	NP_001333528.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RINT1	ENST00000257700.7	TSL:1 MANE Select	c.1891T>G	p.Leu631Val	missense	Exon 13 of 15	ENSP00000257700.2	Q6NUQ1
	EFCAB10	ENST00000480514.6	TSL:1 MANE Select	c.*166A>C		3_prime_UTR	Exon 5 of 5	ENSP00000418678.1	A6NFE3
	RINT1	ENST00000967558.1		c.1996T>G	p.Leu666Val	missense	Exon 13 of 15	ENSP00000637617.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000349 AC: 5 AN: 1432014 Hom.: 0 Cov.: 31 AF XY: 0.00000706 AC XY: 5 AN XY: 708238

African (AFR) AF: 0.00 AC: 0 AN: 32372

American (AMR) AF: 0.00 AC: 0 AN: 39410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39248

South Asian (SAS) AF: 0.00 AC: 0 AN: 82574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 0.00000456 AC: 5 AN: 1095448

Other (OTH) AF: 0.00 AC: 0 AN: 59028

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	6.4
DANN	Benign	0.96
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-2.3
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.23
Sift	Benign	0.19	T
Sift4G	Uncertain	0.019	D
Polyphen		0.96	D
Vest4		0.61
MutPred		0.39		Loss of helix (P = 0.0558)
MVP		0.30
MPC		0.65
ClinPred		0.52	D
GERP RS		-5.0
Varity_R		0.048
gMVP		0.23
Mutation Taster		=73/27	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: rs763828038; hg19: chr7-105205728;