chr14-58353680-G-A

Variant names:

• chr14-58353680-G-A
• NM_002892.4:c.1678G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002892.4(ARID4A):​c.1678G>A​(p.Asp560Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARID4A NM_002892.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.12
• Publications: 0 publications found

Genes affected

ARID4A (HGNC:9885): (AT-rich interaction domain 4A) The protein encoded by this gene is a ubiquitously expressed nuclear protein. It binds directly, with several other proteins, to retinoblastoma protein (pRB) which regulates cell proliferation. pRB represses transcription by recruiting the encoded protein. This protein, in turn, serves as a bridging molecule to recruit HDACs and, in addition, provides a second HDAC-independent repression function. The encoded protein possesses transcriptional repression activity. Multiple alternatively spliced transcripts have been observed for this gene, although not all transcript variants have been fully described. [provided by RefSeq, Jul 2008]

TOMM20L-DT (HGNC:55443): (TOMM20L divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28765953).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002892.4. 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
	ARID4A	NM_002892.4	MANE Select	c.1678G>A	p.Asp560Asn	missense	Exon 17 of 24	NP_002883.3
	ARID4A	NM_023000.3		c.1678G>A	p.Asp560Asn	missense	Exon 17 of 24	NP_075376.2	P29374-2
	ARID4A	NM_023001.3		c.1678G>A	p.Asp560Asn	missense	Exon 17 of 23	NP_075377.2	P29374-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID4A	ENST00000355431.8	TSL:1 MANE Select	c.1678G>A	p.Asp560Asn	missense	Exon 17 of 24	ENSP00000347602.3	P29374-1
	ARID4A	ENST00000417477.2	TSL:1	c.712G>A	p.Asp238Asn	missense	Exon 7 of 10	ENSP00000416053.2	H7C485
	ARID4A	ENST00000941390.1		c.1678G>A	p.Asp560Asn	missense	Exon 17 of 24	ENSP00000611449.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.086	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		8.1
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.17
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.034	D
Polyphen		0.68	P
Vest4		0.19
MutPred		0.17		Gain of relative solvent accessibility (P = 0.09)
MVP		0.29
MPC		0.31
ClinPred		0.97	D
GERP RS		6.1
Varity_R		0.16
gMVP		0.10
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr14-58820398;