Variant 9-34623481-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001017363.4(ARID3C):c.809C>T(p.Thr270Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000026 in 1,541,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

ARID3C
NM_001017363.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

Variant links:

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]

ARID3C links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11316547).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID3C	NM_001017363.4 linkuse as main transcript	c.809C>T	p.Thr270Ile	missense_variant	5/8	ENST00000378909.4	NP_001017363.1	A6NKF2
ARID3C	NM_001371945.2 linkuse as main transcript	c.809C>T	p.Thr270Ile	missense_variant	5/7		NP_001358874.1
ARID3C	XM_047422781.1 linkuse as main transcript	c.1259C>T	p.Thr420Ile	missense_variant	6/9		XP_047278737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID3C	ENST00000378909.4 linkuse as main transcript	c.809C>T	p.Thr270Ile	missense_variant	5/8	2	NM_001017363.4	ENSP00000368189.2		A6NKF2
ARID3C	ENST00000692051.1 linkuse as main transcript	c.809C>T	p.Thr270Ile	missense_variant	5/6			ENSP00000510553.1		A0A8I5QL24

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.20e-7

AC:

AN:

1389054

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

684986

show subpopulations

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:

0.0000134

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2024

The c.809C>T (p.T270I) alteration is located in exon 4 (coding exon 4) of the ARID3C gene. This alteration results from a C to T substitution at nucleotide position 809, causing the threonine (T) at amino acid position 270 to be replaced by an isoleucine (I). 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

0.087

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0065

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.23

M_CAP

Benign

0.021

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.65

REVEL

Benign

0.045

Sift

Benign

0.056

Sift4G

Uncertain

0.059

Polyphen

0.40

Vest4

0.16

MutPred

0.21

Loss of glycosylation at T270 (P = 0.0046);

MVP

0.13

MPC

0.29

ClinPred

0.10

GERP RS

2.4

Varity_R

0.049

gMVP

0.27

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over