Genetic Variant APBB1IP:p.Lys174Asn (chr10-26503265-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_019043.4(APBB1IP):c.522G>C(p.Lys174Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,178 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

APBB1IP
NM_019043.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.537

Variant links:

Genes affected

APBB1IP (HGNC:17379): (amyloid beta precursor protein binding family B member 1 interacting protein) Predicted to be involved in signal transduction. Predicted to act upstream of or within T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell and positive regulation of cell adhesion. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

APBB1IP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38654324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBB1IP	NM_019043.4 link	c.522G>C	p.Lys174Asn	missense_variant	Exon 6 of 15	ENST00000376236.9	NP_061916.3	Q7Z5R6-1
APBB1IP	XM_011519514.3 link	c.522G>C	p.Lys174Asn	missense_variant	Exon 6 of 14		XP_011517816.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APBB1IP	ENST00000376236.9 link	c.522G>C	p.Lys174Asn	missense_variant	Exon 6 of 15	5	NM_019043.4	ENSP00000365411.4		Q7Z5R6-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.522G>C (p.K174N) alteration is located in exon 6 (coding exon 4) of the APBB1IP gene. This alteration results from a G to C substitution at nucleotide position 522, causing the lysine (K) at amino acid position 174 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

Pathogenic

0.82

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.036

Eigen

Benign

0.12

Eigen_PC

Benign

0.090

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.069

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.45

MutationAssessor

Uncertain

2.8

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.30

Sift

Benign

0.062

Sift4G

Benign

0.072

Polyphen

1.0

Vest4

0.44

MutPred

0.24

Loss of methylation at K174 (P = 0.044);

MVP

0.72

MPC

1.5

ClinPred

0.96

GERP RS

1.8

Varity_R

0.32

gMVP

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over