Genetic Variant ATRIP:p.Pro15Pro (chr3-48446890-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_130384.3(ATRIP):c.45C>T(p.Pro15Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000804 in 1,243,150 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. P15P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

ATRIP
NM_130384.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.400

Publications

0 publications found

Variant links:

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 links:

ATRIP-TREX1 (HGNC:):

ATRIP-TREX1 links:

CCDC51 (HGNC:25714): (coiled-coil domain containing 51) Enables mitochondrial ATP-gated potassium channel activity. Involved in potassium ion transmembrane transport. Is integral component of mitochondrial inner membrane. Part of mitochondrial ATP-gated potassium channel complex. [provided by Alliance of Genome Resources, Apr 2022]

CCDC51 links:

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ACMG classification

Classification was made for transcript

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=-0.62).

BP6

Variant 3-48446890-C-T is Benign according to our data. Variant chr3-48446890-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3694829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.4 with no splicing effect.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATRIP	NM_130384.3	MANE Select	c.45C>T	p.Pro15Pro	synonymous	Exon 1 of 13	NP_569055.1	Q8WXE1-1
ATRIP	NM_032166.4		c.45C>T	p.Pro15Pro	synonymous	Exon 1 of 12	NP_115542.2
ATRIP	NM_001271022.2		c.-218+91C>T		intron	N/A	NP_001257951.1	Q8WXE1-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATRIP	ENST00000320211.10	TSL:1 MANE Select	c.45C>T	p.Pro15Pro	synonymous	Exon 1 of 13	ENSP00000323099.3	Q8WXE1-1
ATRIP	ENST00000346691.9	TSL:1	c.45C>T	p.Pro15Pro	synonymous	Exon 1 of 12	ENSP00000302338.5	Q8WXE1-2
ATRIP	ENST00000949799.1		c.45C>T	p.Pro15Pro	synonymous	Exon 1 of 14	ENSP00000619858.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.04e-7

AC:

AN:

1243150

Hom.:

Cov.:

AF XY:

0.00000165

AC XY:

AN XY:

607148

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25126

American (AMR)

AF:

0.00

AC:

AN:

14930

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16532

East Asian (EAS)

AF:

0.00

AC:

AN:

30456

South Asian (SAS)

AF:

0.00

AC:

AN:

48888

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43158

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3726

European-Non Finnish (NFE)

AF:

9.90e-7

AC:

AN:

1010024

Other (OTH)

AF:

0.00

AC:

AN:

50310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.4

(source)

DANN

Benign

0.89

PhyloP100

-0.40

PromoterAI

0.050

Neutral

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over