7-105565611-T-A

Variant names:

• chr7-105565611-T-A
• rs1060503047
• NM_021930.6:c.2149T>A

Variant summary

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

The NM_001355530.2(EFCAB10):​c.388A>T​(p.Lys130*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EFCAB10 NM_001355530.2 stop_gained
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 6.58
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001355530.2. 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.2149T>A	p.Ser717Thr	missense	Exon 14 of 15	NP_068749.3
	EFCAB10	NM_001355526.2	MANE Select	c.384-164A>T		intron	N/A	NP_001342455.1	A6NFE3
	EFCAB10	NM_001355530.2		c.388A>T	p.Lys130*	stop_gained	Exon 5 of 5	NP_001342459.1	J3KR52

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RINT1	ENST00000257700.7	TSL:1 MANE Select	c.2149T>A	p.Ser717Thr	missense	Exon 14 of 15	ENSP00000257700.2	Q6NUQ1
	EFCAB10	ENST00000480514.6	TSL:1 MANE Select	c.384-164A>T		intron	N/A	ENSP00000418678.1	A6NFE3
	EFCAB10	ENST00000485614.5	TSL:5	c.388A>T	p.Lys130*	stop_gained	Exon 5 of 5	ENSP00000417841.1	J3KR52

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

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
AlphaMissense	Benign	0.11
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.96	D
PhyloP100		6.6
Vest4		0.071
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.37
Mutation Taster		=52/148	disease causing

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: rs1060503047; hg19: chr7-105206058;