9-34622392-A-G

Variant names:

• chr9-34622392-A-G
• rs3808869
• NM_001017363.4:c.1003T>C

Variant summary

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

The NM_001017363.4(ARID3C):​c.1003T>C​(p.Cys335Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,402 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ARID3C NM_001017363.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 27 publications found

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]

ENSG00000294750 (HGNC:):

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=0.0473392).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017363.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID3C	NM_001017363.4	MANE Select	c.1003T>C	p.Cys335Arg	missense	Exon 6 of 8	NP_001017363.1
	ARID3C	NM_001371945.2		c.866-283T>C		intron	N/A	NP_001358874.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID3C	ENST00000378909.4	TSL:2 MANE Select	c.1003T>C	p.Cys335Arg	missense	Exon 6 of 8	ENSP00000368189.2
	ARID3C	ENST00000692051.1		c.866-283T>C		intron	N/A	ENSP00000510553.1
	ENSG00000294750	ENST00000725698.1		n.647-204A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249686 AF XY: 0.00000741

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460402 Hom.: 0 Cov.: 74 AF XY: 0.00000138 AC XY: 1 AN XY: 726498

African (AFR) AF: 0.00 AC: 0 AN: 33348

American (AMR) AF: 0.00 AC: 0 AN: 44350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26050

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111424

Other (OTH) AF: 0.00 AC: 0 AN: 60310

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	17
DANN	Benign	0.80
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.052
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.43	N
REVEL	Benign	0.0080
Sift	Benign	0.35	T
Sift4G	Benign	0.38	T
Polyphen		0.12	B
Vest4		0.095
MutPred		0.23		Gain of methylation at C335 (P = 0.015)
MVP		0.13
MPC		0.46
ClinPred		0.079	T
GERP RS		0.29
Varity_R		0.098
gMVP		0.49
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs3808869; hg19: chr9-34622389;