9-34623692-A-T

Variant names:

• chr9-34623692-A-T
• rs149879108
• NM_001017363.4:c.598T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_Strong BS2

The NM_001017363.4(ARID3C):​c.598T>A​(p.Tyr200Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000495 in 1,414,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: ARID3C NM_001017363.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.80

Genes affected

ARID3C (HGNC:21209): (AT-rich interaction domain 3C) This gene is a member of the ARID (AT-rich interaction domain) family of proteins. The ARID domain is a helix-turn-helix motif-based DNA-binding domain. ARID family members have roles in embryonic patterning, cell lineage gene regulation, cell cycle control, transcriptional regulation and possibly in chromatin structure modification. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.942
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID3C	NM_001017363.4	c.598T>A	p.Tyr200Asn	missense_variant	Exon 5 of 8	ENST00000378909.4	NP_001017363.1
ARID3C	NM_001371945.2	c.598T>A	p.Tyr200Asn	missense_variant	Exon 5 of 7		NP_001358874.1
ARID3C	XM_047422781.1	c.1048T>A	p.Tyr350Asn	missense_variant	Exon 6 of 9		XP_047278737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID3C	ENST00000378909.4	c.598T>A	p.Tyr200Asn	missense_variant	Exon 5 of 8	2	NM_001017363.4	ENSP00000368189.2
ARID3C	ENST00000692051.1	c.598T>A	p.Tyr200Asn	missense_variant	Exon 5 of 6			ENSP00000510553.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000218 AC: 4 AN: 183622 Hom.: 0 AF XY: 0.0000197 AC XY: 2 AN XY: 101738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000497

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000495 AC: 7 AN: 1414522 Hom.: 0 Cov.: 31 AF XY: 0.00000285 AC XY: 2 AN XY: 700882

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000550

Gnomad4 OTH exome AF: 0.0000171

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.0000250 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.90
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.66	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	0.63	D
MutationAssessor	Pathogenic	3.4	M
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-8.5	D
REVEL	Pathogenic	0.83
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.83
MVP		0.72
MPC		1.2
ClinPred		0.91	D
GERP RS		5.5
Varity_R		0.89
gMVP		0.91

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: rs149879108; hg19: chr9-34623689;