10-26501110-A-G

Position:

• chr10-26501110-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019043.4(APBB1IP):​c.452A>G​(p.Gln151Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: APBB1IP NM_019043.4 missense, splice_region
• Scores: Splicing: ADA: 0.06902
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09387234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APBB1IP	NM_019043.4	c.452A>G	p.Gln151Arg	missense_variant, splice_region_variant	5/15	ENST00000376236.9	NP_061916.3
APBB1IP	XM_011519514.3	c.452A>G	p.Gln151Arg	missense_variant, splice_region_variant	5/14		XP_011517816.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APBB1IP	ENST00000356785.4	c.452A>G	p.Gln151Arg	missense_variant	5/5	1		ENSP00000349237.4
APBB1IP	ENST00000376236.9	c.452A>G	p.Gln151Arg	missense_variant, splice_region_variant	5/15	5	NM_019043.4	ENSP00000365411.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2024

The c.452A>G (p.Q151R) alteration is located in exon 5 (coding exon 3) of the APBB1IP gene. This alteration results from a A to G substitution at nucleotide position 452, causing the glutamine (Q) at amino acid position 151 to be replaced by an arginine (R). 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	0.062
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.029	T;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.50
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.090	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.12
Sift	Benign	0.069	T;D
Sift4G	Benign	0.089	T;T
Polyphen		0.0010	B;.
Vest4		0.24
MutPred		0.076		Gain of glycosylation at S150 (P = 0.1231);Gain of glycosylation at S150 (P = 0.1231);
MVP		0.43
MPC		0.53
ClinPred		0.18	T
GERP RS		-0.98
Varity_R		0.037
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.069
dbscSNV1_RF	Benign	0.30
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-26790039;