rs202082690

Variant names:

• chr15-72661322-G-A
• rs202082690
• NM_018652.5:c.623G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-72661322-G-A
• chr15-72661322-G-C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_018652.5(GOLGA6B):​c.623G>A​(p.Arg208Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00649 in 151,946 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0065 (1 hom., cov: 24)
  • Exomes 𝑓: 0.0083 (26 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6B NM_018652.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.978
• Publications: 3 publications found

Genes affected

GOLGA6B (HGNC:32205): (golgin A6 family member B) This gene is found in a large, low copy repeat sequence or duplicon that is found in multiple copies, which are greater than 90% similar, on chromosome 15. Duplicons are associated with deletions, inversions and other chromosomal rearrangements that underlie genomic disease. This gene is a member of the golgin gene family, whose protein products localize to the Golgi apparatus. The majority of the related gene copies are thought to be transcribed pseudogenes. It is not known whether this gene is a pseudogene or if it encodes a golgin protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0055083334).
• BP6: Variant 15-72661322-G-A is Benign according to our data. Variant chr15-72661322-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3341557.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018652.5. 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
	GOLGA6B	NM_018652.5	MANE Select	c.623G>A	p.Arg208Gln	missense	Exon 8 of 18	NP_061122.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6B	ENST00000421285.4	TSL:1 MANE Select	c.623G>A	p.Arg208Gln	missense	Exon 8 of 18	ENSP00000408132.3	A6NDN3
	GOLGA6B	ENST00000909077.1		c.617G>A	p.Arg206Gln	missense	Exon 8 of 18	ENSP00000579136.1

Frequencies

GnomAD3 genomes AF: 0.00649 AC: 986 AN: 151828 Hom.: 1 Cov.: 24

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.00301

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00476 AC: 1171 AN: 245914 AF XY: 0.00483

Gnomad AFR exome AF: 0.00138

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.00951

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.00228

Gnomad NFE exome AF: 0.00758

Gnomad OTH exome AF: 0.00596

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00831 AC: 12068 AN: 1452372 Hom.: 26 Cov.: 32 AF XY: 0.00847 AC XY: 6123 AN XY: 722558

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00126 AC: 42 AN: 33434

American (AMR) AF: 0.00253 AC: 113 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 308 AN: 26030

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39690

South Asian (SAS) AF: 0.00433 AC: 372 AN: 85980

European-Finnish (FIN) AF: 0.00379 AC: 199 AN: 52482

Middle Eastern (MID) AF: 0.00608 AC: 34 AN: 5592

European-Non Finnish (NFE) AF: 0.00953 AC: 10528 AN: 1104460

Other (OTH) AF: 0.00784 AC: 471 AN: 60066

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00649 AC: 986 AN: 151946 Hom.: 1 Cov.: 24 AF XY: 0.00595 AC XY: 442 AN XY: 74336

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00150 AC: 62 AN: 41446

American (AMR) AF: 0.00301 AC: 46 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3466

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5196

South Asian (SAS) AF: 0.00518 AC: 25 AN: 4824

European-Finnish (FIN) AF: 0.00301 AC: 32 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0111 AC: 752 AN: 67790

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0105 Hom.: 0

ExAC AF: 0.00776 AC: 938

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.3
DANN	Benign	0.60
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0055	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.93	L
PhyloP100		0.98
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.91	N
REVEL	Benign	0.038
Sift	Benign	0.54	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.21
MVP		0.030
ClinPred		0.0019	T
GERP RS		-0.78
Varity_R		0.025
gMVP		0.22
Mutation Taster		=98/2	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: rs202082690; hg19: chr15-72953663; COSMIC: COSV69770093; COSMIC: COSV69770093;