chr3-97785085-G-A

Variant names:

• chr3-97785085-G-A
• rs200081059
• NM_001278293.3:c.349+36G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001278293.3(ARL6):​c.349+36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00701 in 1,526,424 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0065 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0071 (63 hom.)
• Consequence: ARL6 NM_001278293.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.690
• Publications: 0 publications found

Genes affected

ARL6 (HGNC:13210): (ADP ribosylation factor like GTPase 6) The protein encoded by this gene belongs to the ARF-like (ADP ribosylation factor-like) sub-family of the ARF family of GTP-binding proteins which are involved in regulation of intracellular traffic. Mutations in this gene are associated with Bardet-Biedl syndrome (BBS). A vision-specific transcript, encoding long isoform BBS3L, has been described (PMID: 20333246). [provided by RefSeq, Apr 2016]

ARL6 Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 55

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-97785085-G-A is Benign according to our data. Variant chr3-97785085-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 262016.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00649 (985/151842) while in subpopulation NFE AF = 0.0098 (665/67826). AF 95% confidence interval is 0.00919. There are 6 homozygotes in GnomAd4. There are 479 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278293.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL6	NM_001278293.3	MANE Select	c.349+36G>A		intron	N/A	NP_001265222.1	Q9H0F7-1
	ARL6	NM_001323513.2		c.349+36G>A		intron	N/A	NP_001310442.1	Q9H0F7-2
	ARL6	NM_032146.5		c.349+36G>A		intron	N/A	NP_115522.1	Q9H0F7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL6	ENST00000463745.6	TSL:2 MANE Select	c.349+36G>A		intron	N/A	ENSP00000419619.1	Q9H0F7-1
	ARL6	ENST00000493990.5	TSL:1	n.349+36G>A		intron	N/A	ENSP00000418057.1	Q9H0F7-1
	ARL6	ENST00000496713.1	TSL:1	n.587+36G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00649 AC: 985 AN: 151726 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0147

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00980

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00667 AC: 1670 AN: 250422 AF XY: 0.00650

Gnomad AFR exome AF: 0.000927

Gnomad AMR exome AF: 0.00212

Gnomad ASJ exome AF: 0.0214

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0140

Gnomad NFE exome AF: 0.00898

Gnomad OTH exome AF: 0.00672

GnomAD4 exome AF: 0.00707 AC: 9721 AN: 1374582 Hom.: 63 Cov.: 21 AF XY: 0.00703 AC XY: 4847 AN XY: 689258

African (AFR) AF: 0.000600 AC: 19 AN: 31688

American (AMR) AF: 0.00209 AC: 93 AN: 44522

Ashkenazi Jewish (ASJ) AF: 0.0235 AC: 598 AN: 25488

East Asian (EAS) AF: 0.00 AC: 0 AN: 39100

South Asian (SAS) AF: 0.000154 AC: 13 AN: 84370

European-Finnish (FIN) AF: 0.0143 AC: 760 AN: 53244

Middle Eastern (MID) AF: 0.00196 AC: 11 AN: 5620

European-Non Finnish (NFE) AF: 0.00759 AC: 7841 AN: 1033162

Other (OTH) AF: 0.00673 AC: 386 AN: 57388

GnomAD4 genome AF: 0.00649 AC: 985 AN: 151842 Hom.: 6 Cov.: 32 AF XY: 0.00646 AC XY: 479 AN XY: 74202

African (AFR) AF: 0.00118 AC: 49 AN: 41460

American (AMR) AF: 0.00151 AC: 23 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 80 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.0147 AC: 155 AN: 10542

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.00980 AC: 665 AN: 67826

Other (OTH) AF: 0.00427 AC: 9 AN: 2108

Alfa AF: 0.0103 Hom.: 2

Bravo AF: 0.00513

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.31
DANN	Benign	0.56
PhyloP100		-0.69
PromoterAI		-0.016	Neutral
Mutation Taster		=100/0	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: rs200081059; hg19: chr3-97503929;