chr10-26533515-C-T

Variant names:

• chr10-26533515-C-T
• NM_019043.4:c.890C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019043.4(APBB1IP):​c.890C>T​(p.Ser297Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,445,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: APBB1IP NM_019043.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.206
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05419591).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019043.4. 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
	APBB1IP	NM_019043.4	MANE Select	c.890C>T	p.Ser297Phe	missense	Exon 9 of 15	NP_061916.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APBB1IP	ENST00000376236.9	TSL:5 MANE Select	c.890C>T	p.Ser297Phe	missense	Exon 9 of 15	ENSP00000365411.4	Q7Z5R6-1
	APBB1IP	ENST00000718302.1		c.890C>T	p.Ser297Phe	missense	Exon 9 of 15	ENSP00000520735.1	Q7Z5R6-1
	APBB1IP	ENST00000872270.1		c.890C>T	p.Ser297Phe	missense	Exon 8 of 14	ENSP00000542329.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1445768 Hom.: 0 Cov.: 28 AF XY: 0.00000278 AC XY: 2 AN XY: 719148

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32662

American (AMR) AF: 0.00 AC: 0 AN: 42328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25612

East Asian (EAS) AF: 0.00 AC: 0 AN: 38840

South Asian (SAS) AF: 0.00 AC: 0 AN: 83118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5440

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1104962

Other (OTH) AF: 0.00 AC: 0 AN: 59692

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.0
DANN	Benign	0.28
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.21
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.013
Sift	Benign	0.69	T
Sift4G	Benign	0.20	T
Polyphen		0.0080	B
Vest4		0.15
MutPred		0.43		Loss of disorder (P = 0.0281)
MVP		0.30
MPC		0.53
ClinPred		0.019	T
GERP RS		0.86
Varity_R		0.026
gMVP		0.28
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr10-26822444; COSMIC: COSV104691810;