chr15-23443797-A-G

Variant names:

• chr15-23443797-A-G
• rs4778531
• NM_001304388.2:c.571T>C
• GOLGA6L2 p.Trp191Arg

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304388.2(GOLGA6L2):​c.571T>C​(p.Trp191Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 1,538,416 control chromosomes in the GnomAD database, including 559,609 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.81 (50460 hom., cov: 33)
  • Exomes 𝑓: 0.86 (509149 hom.)
• Consequence: GOLGA6L2 NM_001304388.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2194167E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304388.2. 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
	GOLGA6L2	NM_001304388.2	MANE Select	c.571T>C	p.Trp191Arg	missense	Exon 5 of 8	NP_001291317.1	Q8N9W4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6L2	ENST00000567107.6	TSL:5 MANE Select	c.571T>C	p.Trp191Arg	missense	Exon 5 of 8	ENSP00000454407.1	Q8N9W4-3
	GOLGA6L2	ENST00000566571.5	TSL:5	n.541T>C		non_coding_transcript_exon	Exon 4 of 7	ENSP00000456523.1	H3BS38

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122905 AN: 152050 Hom.: 50435 Cov.: 33

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.866

Gnomad OTH AF: 0.833

GnomAD2 exomes AF: 0.849 AC: 123093 AN: 144922 AF XY: 0.849

Gnomad AFR exome AF: 0.645

Gnomad AMR exome AF: 0.863

Gnomad ASJ exome AF: 0.843

Gnomad EAS exome AF: 0.871

Gnomad FIN exome AF: 0.904

Gnomad NFE exome AF: 0.865

Gnomad OTH exome AF: 0.864

GnomAD4 exome AF: 0.856 AC: 1186717 AN: 1386246 Hom.: 509149 Cov.: 44 AF XY: 0.856 AC XY: 585598 AN XY: 684288

African (AFR) AF: 0.644 AC: 20365 AN: 31646

American (AMR) AF: 0.867 AC: 31184 AN: 35984

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 21168 AN: 25172

East Asian (EAS) AF: 0.849 AC: 30480 AN: 35888

South Asian (SAS) AF: 0.829 AC: 65742 AN: 79336

European-Finnish (FIN) AF: 0.905 AC: 30979 AN: 34238

Middle Eastern (MID) AF: 0.854 AC: 4867 AN: 5696

European-Non Finnish (NFE) AF: 0.864 AC: 932747 AN: 1080138

Other (OTH) AF: 0.846 AC: 49185 AN: 58148

GnomAD4 genome AF: 0.808 AC: 122978 AN: 152170 Hom.: 50460 Cov.: 33 AF XY: 0.811 AC XY: 60342 AN XY: 74394

African (AFR) AF: 0.651 AC: 27023 AN: 41490

American (AMR) AF: 0.867 AC: 13265 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2940 AN: 3466

East Asian (EAS) AF: 0.865 AC: 4457 AN: 5154

South Asian (SAS) AF: 0.832 AC: 4013 AN: 4826

European-Finnish (FIN) AF: 0.903 AC: 9569 AN: 10598

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.866 AC: 58891 AN: 68020

Other (OTH) AF: 0.836 AC: 1769 AN: 2116

Alfa AF: 0.841 Hom.: 111235

Bravo AF: 0.798

Asia WGS AF: 0.844 AC: 2937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.4
DANN	Benign	0.68
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.000050	N
LIST_S2	Benign	0.023	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.13
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	2.2	N
REVEL	Benign	0.040
Sift4G	Benign	0.33	T
Varity_R		0.11
gMVP		0.089
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4778531;

hg19: chr15-23688944;

COSMIC: COSV61473441;