7-105565352-G-T

Variant names:

• chr7-105565352-G-T
• rs139532717
• NM_021930.6:c.1962G>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_021930.6(RINT1):​c.1962G>T​(p.Thr654Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T654T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RINT1 NM_021930.6 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.45
• 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: Benign. The variant received -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 7-105565352-G-T is Benign according to our data. Variant chr7-105565352-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2447101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.45 with no splicing effect.

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.1962G>T	p.Thr654Thr	synonymous	Exon 13 of 15	NP_068749.3
	EFCAB10	NM_001355526.2	MANE Select	c.*95C>A		3_prime_UTR	Exon 5 of 5	NP_001342455.1	A6NFE3
	RINT1	NM_001346599.2		c.1728G>T	p.Thr576Thr	synonymous	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.1962G>T	p.Thr654Thr	synonymous	Exon 13 of 15	ENSP00000257700.2	Q6NUQ1
	EFCAB10	ENST00000480514.6	TSL:1 MANE Select	c.*95C>A		3_prime_UTR	Exon 5 of 5	ENSP00000418678.1	A6NFE3
	RINT1	ENST00000967558.1		c.2067G>T	p.Thr689Thr	synonymous	Exon 13 of 15	ENSP00000637617.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461868 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

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
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.010
DANN	Benign	0.37
PhyloP100		-6.4

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: rs139532717; hg19: chr7-105205799;