chr7-105565588-C-G

Variant names:

• chr7-105565588-C-G
• rs1060503048
• NM_021930.6:c.2126C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021930.6(RINT1):​c.2126C>G​(p.Thr709Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 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. T709I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RINT1 NM_021930.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• 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]

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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057053417).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RINT1	NM_021930.6	MANE Select	c.2126C>G	p.Thr709Ser	missense	Exon 14 of 15	NP_068749.3
	EFCAB10	NM_001355526.2	MANE Select	c.384-141G>C		intron	N/A	NP_001342455.1
	RINT1	NM_001346599.2		c.1892C>G	p.Thr631Ser	missense	Exon 14 of 15	NP_001333528.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RINT1	ENST00000257700.7	TSL:1 MANE Select	c.2126C>G	p.Thr709Ser	missense	Exon 14 of 15	ENSP00000257700.2
	EFCAB10	ENST00000480514.6	TSL:1 MANE Select	c.384-141G>C		intron	N/A	ENSP00000418678.1
	EFCAB10	ENST00000485614.5	TSL:5	c.411G>C	p.Glu137Asp	missense	Exon 5 of 5	ENSP00000417841.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Benign	-0.61
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.024
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.1
PROVEAN	Benign	0.010	N
REVEL	Benign	0.079
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.18
MutPred		0.11		Loss of helix (P = 0.0444)
MVP		0.088
MPC		0.0037
ClinPred		0.68	D
GERP RS		5.7
Varity_R		0.11
gMVP		0.11
Mutation Taster		=85/15	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: rs1060503048; hg19: chr7-105206035;