15-22466251-A-G

Variant names:

• chr15-22466251-A-G
• rs562628195
• NM_001396956.1:c.1991A>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001396956.1(GOLGA6L22):​c.1991A>G​(p.Glu664Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (28 hom., cov: 12)
  • Exomes 𝑓: 0.010 (829 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L22 NM_001396956.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0940

Genes affected

GOLGA6L22 (HGNC:50289): (golgin A6 family like 22)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0063911676).
• BP6: Variant 15-22466251-A-G is Benign according to our data. Variant chr15-22466251-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2644963.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 28 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA6L22	NM_001396956.1	c.1991A>G	p.Glu664Gly	missense_variant	Exon 8 of 9	ENST00000622895.2	NP_001383885.1
GOLGA6L22	NM_001396957.1	c.1988A>G	p.Glu663Gly	missense_variant	Exon 8 of 9		NP_001383886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA6L22	ENST00000622895.2	c.1991A>G	p.Glu664Gly	missense_variant	Exon 8 of 9	5	NM_001396956.1	ENSP00000483673.2

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 851 AN: 81224 Hom.: 29 Cov.: 12

Gnomad AFR AF: 0.00187

Gnomad AMI AF: 0.0431

Gnomad AMR AF: 0.00680

Gnomad ASJ AF: 0.000972

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00395

Gnomad FIN AF: 0.0237

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0144

Gnomad OTH AF: 0.00690

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00997 AC: 8258 AN: 828432 Hom.: 829 Cov.: 12 AF XY: 0.00977 AC XY: 4164 AN XY: 426194

Gnomad4 AFR exome AF: 0.00221

Gnomad4 AMR exome AF: 0.00576

Gnomad4 ASJ exome AF: 0.00145

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00195

Gnomad4 FIN exome AF: 0.0375

Gnomad4 NFE exome AF: 0.0105

Gnomad4 OTH exome AF: 0.0116

GnomAD4 genome AF: 0.0105 AC: 850 AN: 81280 Hom.: 28 Cov.: 12 AF XY: 0.0107 AC XY: 419 AN XY: 39110

Gnomad4 AFR AF: 0.00192

Gnomad4 AMR AF: 0.00679

Gnomad4 ASJ AF: 0.000972

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00282

Gnomad4 FIN AF: 0.0237

Gnomad4 NFE AF: 0.0144

Gnomad4 OTH AF: 0.00681

Alfa AF: 0.0119 Hom.: 6

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RP11-467N20.5: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.88
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.0087	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.0064	T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.53	T
Sift4G	Benign	0.24	T
Vest4		0.083
MVP		0.092
ClinPred		0.15	T
Varity_R		0.038
gMVP		0.0057

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

Other links and lift over

dbSNP: rs562628195; hg19: chr15-22743339;