rs4778531

Positions:

• chr15-23443797-A-C
• chr15-23443797-A-G
• chr15-23443797-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001304388.2(GOLGA6L2):​c.571T>G​(p.Trp191Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,386,514 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W191R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07800135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGA6L2	NM_001304388.2	c.571T>G	p.Trp191Gly	missense_variant	5/8	ENST00000567107.6	NP_001291317.1
GOLGA6L2	XM_047432396.1	c.412T>G	p.Trp138Gly	missense_variant	3/6		XP_047288352.1
GOLGA6L2	XM_047432397.1	c.571T>G	p.Trp191Gly	missense_variant	5/11		XP_047288353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLGA6L2	ENST00000567107.6	c.571T>G	p.Trp191Gly	missense_variant	5/8	5	NM_001304388.2	ENSP00000454407	P1
GOLGA6L2	ENST00000566571.5	c.541T>G	p.Trp181Gly	missense_variant, NMD_transcript_variant	4/7	5		ENSP00000456523

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1386514 Hom.: 0 Cov.: 44 AF XY: 0.00000146 AC XY: 1 AN XY: 684400

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000279

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.78
DEOGEN2	Benign	0.0046	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.25	T;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.078	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.16	N;.
REVEL	Benign	0.039
Sift4G	Benign	0.25	T;D
Polyphen		0.020	B;.
Vest4		0.13
MutPred		0.50		Gain of disorder (P = 0.004);.;
MVP		0.030
MPC		0.015
ClinPred		0.033	T
Varity_R		0.13
gMVP		0.046

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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;