rs1438000639

Variant names:

• chr14-58346423-A-C
• rs1438000639
• NM_002892.4:c.992A>C

Your query was ambiguous. Multiple possible variants found:

• chr14-58346423-A-C
• chr14-58346423-A-G

Variant summary

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

The NM_002892.4(ARID4A):​c.992A>C​(p.Asn331Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 29)
• Consequence: ARID4A NM_002892.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.32

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID4A	NM_002892.4	c.992A>C	p.Asn331Thr	missense_variant	Exon 13 of 24	ENST00000355431.8	NP_002883.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID4A	ENST00000355431.8	c.992A>C	p.Asn331Thr	missense_variant	Exon 13 of 24	1	NM_002892.4	ENSP00000347602.3

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 29

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D;.;.;.;T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D;.;D
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.54	D;D;D;D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.2	L;L;L;L;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-5.2	D;D;D;D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.016	D;D;D;D;D
Sift4G	Uncertain	0.0050	D;T;T;T;D
Polyphen		0.75	P;P;P;P;.
Vest4		0.69
MutPred		0.39		Gain of catalytic residue at P333 (P = 0);Gain of catalytic residue at P333 (P = 0);Gain of catalytic residue at P333 (P = 0);Gain of catalytic residue at P333 (P = 0);.;
MVP		0.65
MPC		0.54
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.51
gMVP		0.47

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

Other links and lift over

dbSNP: rs1438000639; hg19: chr14-58813141;