ATRIP p.Leu612Leu

Variant names:

• chr3-48463832-C-C
• NM_130384.3:c.

Your query was ambiguous. Multiple possible variants found:

• chr3-48463833--
• chr3-48463833-C-T
• chr3-48463835-G-T
• chr3-48463835-G-C
• chr3-48463835-G-A
• chr3-48463833-CTG-TTA

Variant summary

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

The NM_130384.3(ATRIP):​c. variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATRIP NM_130384.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221
• Publications: 0 publications found

Genes affected

ATRIP (HGNC:33499): (ATR interacting protein) This gene encodes an essential component of the DNA damage checkpoint. The encoded protein binds to single-stranded DNA coated with replication protein A. The protein also interacts with the ataxia telangiectasia and Rad3 related protein kinase, resulting in its accumulation at intranuclear foci induced by DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2012]

ATRIP Gene-Disease associations (from GenCC):

• breast cancer

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• Seckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary breast carcinoma

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ATRIP-TREX1 (HGNC:):

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_130384.3. 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
	ATRIP	NM_130384.3	MANE Select	c.		intron	N/A	NP_569055.1	Q8WXE1-1
	ATRIP	NM_032166.4		c.		intron	N/A	NP_115542.2
	ATRIP	NM_001271023.2		c.		intron	N/A	NP_001257952.1	Q8WXE1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRIP	ENST00000320211.10	TSL:1 MANE Select	c.		splice_donor intron	N/A	ENSP00000323099.3	Q8WXE1-1
	ATRIP	ENST00000346691.9	TSL:1	c.		splice_donor intron	N/A	ENSP00000302338.5	Q8WXE1-2
	ATRIP	ENST00000412052.4	TSL:1	c.		splice_donor intron	N/A	ENSP00000400930.1	Q8WXE1-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.22

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-48505231;