Variant 6-116877485-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The NM_173560.4(RFX6):c.210G>A(p.Gly70=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000398 in 1,558,672 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 1 hom. )

Consequence

RFX6
NM_173560.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0600

Variant links:

Genes affected

RFX6 (HGNC:21478): (regulatory factor X6) The nuclear protein encoded by this gene is a member of the regulatory factor X (RFX) family of transcription factors. Studies in mice suggest that this gene is specifically required for the differentiation of islet cells for the production of insulin, but not for the differentiation of pancreatic polypeptide-producing cells. It regulates the transcription factors involved in beta-cell maturation and function, thus, restricting the expression of the beta-cell differentiation and specification genes. Mutations in this gene are associated with Mitchell-Riley syndrome, which is characterized by neonatal diabetes with pancreatic hypoplasia, duodenal and jejunal atresia, and gall bladder agenesis.[provided by RefSeq, Sep 2010]

RFX6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 6-116877485-G-A is Benign according to our data. Variant chr6-116877485-G-A is described in ClinVar as [Benign]. Clinvar id is 1170402.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-116877485-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.06 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000381 (58/152332) while in subpopulation SAS AF= 0.00145 (7/4832). AF 95% confidence interval is 0.000679. There are 0 homozygotes in gnomad4. There are 30 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFX6	NM_173560.4 linkuse as main transcript	c.210G>A	p.Gly70=	synonymous_variant	1/19	ENST00000332958.3	NP_775831.2
RFX6	XM_011535589.2 linkuse as main transcript	c.210G>A	p.Gly70=	synonymous_variant	1/18		XP_011533891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFX6	ENST00000332958.3 linkuse as main transcript	c.210G>A	p.Gly70=	synonymous_variant	1/19	1	NM_173560.4	ENSP00000332208	P1
RFX6	ENST00000487683.5 linkuse as main transcript	n.274G>A		non_coding_transcript_exon_variant	1/14	5

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000674

AC:

109

AN:

161708

Hom.:

AF XY:

0.000776

AC XY:

AN XY:

86304

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000585

Gnomad ASJ exome

AF:

0.00259

Gnomad EAS exome

AF:

0.0000831

Gnomad SAS exome

AF:

0.00181

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000424

Gnomad OTH exome

AF:

0.000447

GnomAD4 exome

AF:

0.000400

AC:

563

AN:

1406340

Hom.:

Cov.:

AF XY:

0.000452

AC XY:

314

AN XY:

694212

show subpopulations

Gnomad4 AFR exome

AF:

0.0000312

Gnomad4 AMR exome

AF:

0.000516

Gnomad4 ASJ exome

AF:

0.00314

Gnomad4 EAS exome

AF:

0.0000274

Gnomad4 SAS exome

AF:

0.00186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000242

Gnomad4 OTH exome

AF:

0.000737

GnomAD4 genome

AF:

0.000381

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000581

Hom.:

Bravo

AF:

0.000446

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 2023

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.8

DANN

Benign

0.89

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