Genetic Variant ATF7IP2:p.Ser48Asn (chr16-10430763-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001393719.1(ATF7IP2):c.143G>A(p.Ser48Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ATF7IP2
NM_001393719.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.539

Variant links:

Genes affected

ATF7IP2 (HGNC:20397): (activating transcription factor 7 interacting protein 2) Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ATF7IP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF7IP2	NM_001393719.1 link	c.143G>A	p.Ser48Asn	missense_variant	Exon 5 of 14	ENST00000562102.6	NP_001380648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF7IP2	ENST00000562102.6 link	c.143G>A	p.Ser48Asn	missense_variant	Exon 5 of 14	4	NM_001393719.1	ENSP00000457731.2		Q5U623-1H3BUP1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461806

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.143G>A (p.S48N) alteration is located in exon 2 (coding exon 1) of the ATF7IP2 gene. This alteration results from a G to A substitution at nucleotide position 143, causing the serine (S) at amino acid position 48 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0053

T;.;.;.;.;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.60

.;.;T;T;T;T

M_CAP

Benign

0.0081

MetaRNN

Benign

0.11

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L;.;.;L;L

PrimateAI

Benign

0.37

PROVEAN

Benign

0.020

N;N;N;N;N;N

REVEL

Benign

0.079

Sift

Benign

0.24

T;T;T;T;T;T

Sift4G

Uncertain

0.015

D;D;T;T;D;D

Polyphen

0.047

B;B;.;.;B;B

Vest4

0.088

MutPred

0.056

Loss of glycosylation at S48 (P = 0.0644);Loss of glycosylation at S48 (P = 0.0644);Loss of glycosylation at S48 (P = 0.0644);Loss of glycosylation at S48 (P = 0.0644);Loss of glycosylation at S48 (P = 0.0644);Loss of glycosylation at S48 (P = 0.0644);

MVP

0.14

MPC

0.011

ClinPred

0.12

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.041

gMVP

0.040

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.28

Position offset: 2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over