15-23443797-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA6L2	NM_001304388.2	c.571T>C	p.Trp191Arg	missense_variant	Exon 5 of 8	ENST00000567107.6	NP_001291317.1
GOLGA6L2	XM_047432396.1	c.412T>C	p.Trp138Arg	missense_variant	Exon 3 of 6		XP_047288352.1
GOLGA6L2	XM_047432397.1	c.571T>C	p.Trp191Arg	missense_variant	Exon 5 of 11		XP_047288353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA6L2	ENST00000567107.6	c.571T>C	p.Trp191Arg	missense_variant	Exon 5 of 8	5	NM_001304388.2	ENSP00000454407.1
GOLGA6L2	ENST00000566571.5	n.541T>C		non_coding_transcript_exon_variant	Exon 4 of 7	5		ENSP00000456523.1

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

GnomAD3 exomes AF: 0.849 AC: 123093 AN: 144922 Hom.: 52504 AF XY: 0.849 AC XY: 66381 AN XY: 78196

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 SAS exome AF: 0.829

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

Gnomad4 AFR exome AF: 0.644

Gnomad4 AMR exome AF: 0.867

Gnomad4 ASJ exome AF: 0.841

Gnomad4 EAS exome AF: 0.849

Gnomad4 SAS exome AF: 0.829

Gnomad4 FIN exome AF: 0.905

Gnomad4 NFE exome AF: 0.864

Gnomad4 OTH exome AF: 0.846

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

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.867

Gnomad4 ASJ AF: 0.848

Gnomad4 EAS AF: 0.865

Gnomad4 SAS AF: 0.832

Gnomad4 FIN AF: 0.903

Gnomad4 NFE AF: 0.866

Gnomad4 OTH AF: 0.836

Alfa AF: 0.854 Hom.: 80361

Bravo AF: 0.798

TwinsUK AF: 0.870 AC: 3226

ALSPAC AF: 0.865 AC: 3334

ExAC AF: 0.800 AC: 72893

Asia WGS AF: 0.844 AC: 2937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
MetaRNN	Benign	0.0000012	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	2.2	N;.
REVEL	Benign	0.040
Sift4G	Benign	0.33	T;T
Polyphen		0.020	B;.
Vest4		0.092
MutPred		0.42		Gain of disorder (P = 0.0022);.;
MPC		0.015
ClinPred		0.0022	T
Varity_R		0.11
gMVP		0.089

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: rs4778531; hg19: chr15-23688944; COSMIC: COSV61473441;