chr2-96551394-C-T

Position:

• chr2-96551394-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The ENST00000357485.8(ARID5A):​c.866C>T​(p.Ser289Phe) variant causes a missense 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. 15/21 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)
• Consequence: ARID5A ENST00000357485.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.485

Genes affected

ARID5A (HGNC:17361): (AT-rich interaction domain 5A) Members of the ARID protein family, including ARID5A, have diverse functions but all appear to play important roles in development, tissue-specific gene expression, and regulation of cell growth (Patsialou et al., 2005 [PubMed 15640446]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity ARI5A_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0937686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID5A	NM_212481.3	c.866C>T	p.Ser289Phe	missense_variant	7/7	ENST00000357485.8	NP_997646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID5A	ENST00000357485.8	c.866C>T	p.Ser289Phe	missense_variant	7/7	1	NM_212481.3	ENSP00000350078	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Nov 21, 2022

The c.866C>T (p.S289F) alteration is located in exon 7 (coding exon 7) of the ARID5A gene. This alteration results from a C to T substitution at nucleotide position 866, causing the serine (S) at amino acid position 289 to be replaced by a phenylalanine (F). 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	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	T;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.094	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.5	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.083
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.016	D;D
Polyphen		0.092	B;.
Vest4		0.17
MutPred		0.14		Loss of glycosylation at S289 (P = 0.0152);.;
MVP		0.17
MPC		0.38
ClinPred		0.45	T
GERP RS		3.4
Varity_R		0.099
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-97217131;