chr15-20534690-A-C

Position:

• chr15-20534690-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001145004.2(GOLGA6L6):​c.1744T>G​(p.Trp582Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000074 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L6 NM_001145004.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.633

Genes affected

GOLGA6L6 (HGNC:37225): (golgin A6 family like 6)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07124895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGA6L6	NM_001145004.2	c.1744T>G	p.Trp582Gly	missense_variant	8/9	ENST00000619213.1	NP_001138476.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLGA6L6	ENST00000619213.1	c.1744T>G	p.Trp582Gly	missense_variant	8/9	5	NM_001145004.2	ENSP00000480376.1

Frequencies

GnomAD3 genomes AF: 0.000149 AC: 8 AN: 53834 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000115

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000743 AC: 6 AN: 807852 Hom.: 0 Cov.: 23 AF XY: 0.0000103 AC XY: 4 AN XY: 388962

Gnomad4 AFR exome AF: 0.0000584

Gnomad4 AMR exome AF: 0.000220

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000479

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000343

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000149 AC: 8 AN: 53834 Hom.: 0 Cov.: 0 AF XY: 0.000114 AC XY: 3 AN XY: 26242

Gnomad4 AFR AF: 0.000363

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000115

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 04, 2024

The c.1822T>G (p.W608G) alteration is located in exon 8 (coding exon 8) of the GOLGA6L6 gene. This alteration results from a T to G substitution at nucleotide position 1822, causing the tryptophan (W) at amino acid position 608 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	0.19
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.6
DANN	Benign	0.40
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.051	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.58	T
Sift4G	Benign	0.35	T
Vest4		0.15
MVP		0.030
ClinPred		0.067	T
Varity_R		0.11
gMVP		0.0024

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: rs760073321; hg19: chr15-20739928;