15-23129895-T-C

Variant names:

• chr15-23129895-T-C
• rs1595973664
• NM_001001413.3:c.1558A>G

Variant summary

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

The NM_001001413.3(GOLGA6L1):​c.1558A>G​(p.Arg520Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000406 in 147,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 6/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000041 (0 hom., cov: 37)
  • Exomes 𝑓: 0.0000013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L1 NM_001001413.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.26

Genes affected

GOLGA6L1 (HGNC:37444): (golgin A6 family like 1)

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=0.073650986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA6L1	NM_001001413.3	c.1558A>G	p.Arg520Gly	missense_variant	Exon 8 of 9	ENST00000614055.2	NP_001001413.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA6L1	ENST00000614055.2	c.1558A>G	p.Arg520Gly	missense_variant	Exon 8 of 9	5	NM_001001413.3	ENSP00000478478.1

Frequencies

GnomAD3 genomes AF: 0.0000406 AC: 6 AN: 147606 Hom.: 0 Cov.: 37

Gnomad AFR AF: 0.0000248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000205

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000604

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000128 AC: 1 AN: 779618 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 402806

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000189

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000406 AC: 6 AN: 147606 Hom.: 0 Cov.: 37 AF XY: 0.0000417 AC XY: 3 AN XY: 71982

Gnomad4 AFR AF: 0.0000248

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000205

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000604

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1558A>G (p.R520G) alteration is located in exon 8 (coding exon 8) of the GOLGA6L1 gene. This alteration results from a A to G substitution at nucleotide position 1558, causing the arginine (R) at amino acid position 520 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
CADD	Benign	4.6
DANN	Benign	0.22
DEOGEN2	Benign	0.032	T
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.074	T
Sift4G	Uncertain	0.055	T
Vest4		0.15
gMVP		0.018

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: rs1595973664; hg19: -;