9-34623510-C-A

Position:

• chr9-34623510-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001017363.4(ARID3C):​c.780G>T​(p.Gln260His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,409,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ARID3C NM_001017363.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.868

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03742665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID3C	NM_001017363.4	c.780G>T	p.Gln260His	missense_variant	5/8	ENST00000378909.4	NP_001017363.1
ARID3C	NM_001371945.2	c.780G>T	p.Gln260His	missense_variant	5/7		NP_001358874.1
ARID3C	XM_047422781.1	c.1230G>T	p.Gln410His	missense_variant	6/9		XP_047278737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID3C	ENST00000378909.4	c.780G>T	p.Gln260His	missense_variant	5/8	2	NM_001017363.4	ENSP00000368189.2
ARID3C	ENST00000692051.1	c.780G>T	p.Gln260His	missense_variant	5/6			ENSP00000510553.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000213 AC: 3 AN: 1409258 Hom.: 0 Cov.: 31 AF XY: 0.00000287 AC XY: 2 AN XY: 697282

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: 0.00000275

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Oct 09, 2024

The c.780G>T (p.Q260H) alteration is located in exon 4 (coding exon 4) of the ARID3C gene. This alteration results from a G to T substitution at nucleotide position 780, causing the glutamine (Q) at amino acid position 260 to be replaced by a histidine (H). 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	0.077
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.012
DANN	Benign	0.62
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.13
Sift	Benign	0.13	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.069
MutPred		0.20		Loss of glycosylation at P263 (P = 0.1586);
MVP		0.014
MPC		0.24
ClinPred		0.076	T
GERP RS		-5.6
Varity_R		0.058
gMVP		0.21

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: chr9-34623507;