rs776923642

Variant names:

• chr15-72662444-G-A
• rs776923642
• NM_018652.5:c.1040G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-72662444-G-A
• chr15-72662444-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_018652.5(GOLGA6B):​c.1040G>A​(p.Arg347Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.000055 (2 hom., cov: 20)
  • Exomes 𝑓: 0.00013 (6 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6B NM_018652.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.92
• Publications: 2 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.036625475).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.1040G>A	p.Arg347Gln	missense	Exon 11 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.1040G>A	p.Arg347Gln	missense	Exon 11 of 18	ENSP00000408132.3	A6NDN3
	GOLGA6B	ENST00000909077.1		c.1034G>A	p.Arg345Gln	missense	Exon 11 of 18	ENSP00000579136.1

Frequencies

GnomAD3 genomes AF: 0.0000551 AC: 7 AN: 127044 Hom.: 2 Cov.: 20

Gnomad AFR AF: 0.0000831

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: 0.0000700

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000415 AC: 9 AN: 216812 AF XY: 0.0000512

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000711

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000132 AC: 167 AN: 1266718 Hom.: 6 Cov.: 36 AF XY: 0.000111 AC XY: 70 AN XY: 628020

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

African (AFR) AF: 0.00 AC: 0 AN: 30908

American (AMR) AF: 0.00 AC: 0 AN: 39784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20818

East Asian (EAS) AF: 0.0000298 AC: 1 AN: 33520

South Asian (SAS) AF: 0.000115 AC: 8 AN: 69404

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4458

European-Non Finnish (NFE) AF: 0.000160 AC: 155 AN: 969982

Other (OTH) AF: 0.0000575 AC: 3 AN: 52212

⚠️ 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: 0.0000551 AC: 7 AN: 127044 Hom.: 2 Cov.: 20 AF XY: 0.0000489 AC XY: 3 AN XY: 61334

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

African (AFR) AF: 0.0000831 AC: 3 AN: 36098

American (AMR) AF: 0.00 AC: 0 AN: 12656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2676

East Asian (EAS) AF: 0.00 AC: 0 AN: 4094

South Asian (SAS) AF: 0.00 AC: 0 AN: 3380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.0000700 AC: 4 AN: 57148

Other (OTH) AF: 0.00 AC: 0 AN: 1636

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00131091), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000826 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.0
DANN	Benign	0.76
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0063	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.00095	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.63	N
PhyloP100		-2.9
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.010
Sift	Benign	0.36	T
Sift4G	Benign	0.56	T
Polyphen		0.0010	B
Vest4		0.043
MutPred		0.30		Loss of MoRF binding (P = 0.0898)
MVP		0.014
ClinPred		0.053	T
Varity_R		0.032
gMVP		0.075
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: rs776923642; hg19: chr15-72954785;