Variant 9-34621499-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001017363.4(ARID3C):c.1198C>T(p.Pro400Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,544,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

ARID3C
NM_001017363.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0410

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.038083166).

BS2

High AC in GnomAd4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID3C	NM_001017363.4 linkuse as main transcript	c.1198C>T	p.Pro400Ser	missense_variant	8/8	ENST00000378909.4	NP_001017363.1	A6NKF2
ARID3C	NM_001371945.2 linkuse as main transcript	c.1015C>T	p.Pro339Ser	missense_variant	7/7		NP_001358874.1
ARID3C	XM_047422781.1 linkuse as main transcript	c.1648C>T	p.Pro550Ser	missense_variant	9/9		XP_047278737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID3C	ENST00000378909.4 linkuse as main transcript	c.1198C>T	p.Pro400Ser	missense_variant	8/8	2	NM_001017363.4	ENSP00000368189.2		A6NKF2
ARID3C	ENST00000692051.1 linkuse as main transcript	c.*471C>T		3_prime_UTR_variant	6/6			ENSP00000510553.1		A0A8I5QL24

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

151894

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000155

AC:

AN:

187564

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

104062

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.000169

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000453

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000227

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000123

AC:

171

AN:

1392796

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

AN XY:

691824

show subpopulations

Gnomad4 AFR exome

AF:

0.000141

Gnomad4 AMR exome

AF:

0.000148

Gnomad4 ASJ exome

AF:

0.0000428

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000271

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000139

Gnomad4 OTH exome

AF:

0.000157

GnomAD4 genome

AF:

0.000164

AC:

AN:

152012

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000194

Hom.:

Bravo

AF:

0.000125

ExAC

AF:

0.000173

AC:

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

Mar 27, 2023

The c.1198C>T (p.P400S) alteration is located in exon 7 (coding exon 7) of the ARID3C gene. This alteration results from a C to T substitution at nucleotide position 1198, causing the proline (P) at amino acid position 400 to be replaced by a serine (S). 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

0.065

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0058

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.44

M_CAP

Benign

0.0066

MetaRNN

Benign

0.038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.98

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.31

REVEL

Benign

0.027

Sift

Benign

0.51

Sift4G

Benign

0.16

Polyphen

0.056

Vest4

0.34

MVP

0.14

MPC

0.26

ClinPred

0.013

GERP RS

3.5

Varity_R

0.027

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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