15-23440478-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001304388.2(GOLGA6L2):c.1997A>G(p.Glu666Gly) 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 Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L2 NM_001304388.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.488

Genes affected

GOLGA6L2 (HGNC:26695): (golgin A6 family like 2) Predicted to be located in cis-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0062844455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GOLGA6L2	NM_001304388.2	c.1997A>G	p.Glu666Gly	missense_variant	8/8	ENST00000567107.6
GOLGA6L2	XM_047432396.1	c.1838A>G	p.Glu613Gly	missense_variant	6/6
GOLGA6L2	XM_047432397.1	c.1276A>G	p.Lys426Glu	missense_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOLGA6L2	ENST00000567107.6	c.1997A>G	p.Glu666Gly	missense_variant	8/8	5	NM_001304388.2	P1
GOLGA6L2	ENST00000566571.5	c.*1278A>G		3_prime_UTR_variant, NMD_transcript_variant	7/7	5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 13 AN: 19954 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.000234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000821

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000308

Gnomad OTH AF: 0.00420

GnomAD4 exome AF: 0.000135 AC: 28 AN: 207598 Hom.: 0 Cov.: 0 AF XY: 0.000172 AC XY: 18 AN XY: 104518

Gnomad4 AFR exome AF: 0.000145

Gnomad4 AMR exome AF: 0.000188

Gnomad4 ASJ exome AF: 0.00176

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000221

Gnomad4 FIN exome AF: 0.000154

Gnomad4 NFE exome AF: 0.0000886

Gnomad4 OTH exome AF: 0.000231

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000651 AC: 13 AN: 19982 Hom.: 0 Cov.: 0 AF XY: 0.000407 AC XY: 4 AN XY: 9832

Gnomad4 AFR AF: 0.000234

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000821

Gnomad4 NFE AF: 0.000308

Gnomad4 OTH AF: 0.00417

Alfa AF: 0.348 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
Cadd	Benign	11
Dann	Benign	0.90
FATHMM_MKL	Benign	0.00067	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.0063	T
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Benign	-0.63	N
Sift4G	Benign	0.50	T
Vest4		0.12
MVP		0.030
MPC		0.014
Varity_R		0.073
gMVP		0.032

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: rs372736971; hg19: chr15-23685625; COSMIC: COSV61481438;