15-82342859-C-T

Variant names:

• chr15-82342859-C-T
• NM_001164465.3:c.1486G>A

Variant summary

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

The NM_001164465.3(GOLGA6L10):​c.1486G>A​(p.Glu496Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 54)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L10 NM_001164465.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.190

Genes affected

GOLGA6L10 (HGNC:37228): (golgin A6 family like 10)

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=0.15849277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA6L10	NM_001164465.3	c.1486G>A	p.Glu496Lys	missense_variant	Exon 9 of 9	ENST00000610657.2	NP_001157937.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA6L10	ENST00000610657.2	c.1486G>A	p.Glu496Lys	missense_variant	Exon 9 of 9	2	NM_001164465.3	ENSP00000479362.1
GOLGA6L10	ENST00000621197.4	c.1237G>A	p.Glu413Lys	missense_variant	Exon 10 of 10	5		ENSP00000484254.2

Frequencies

GnomAD3 genomes Cov.: 54

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.86e-7 AC: 1 AN: 1457886 Hom.: 0 Cov.: 119 AF XY: 0.00 AC XY: 0 AN XY: 725264

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 54

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1357G>A (p.E453K) alteration is located in exon 9 (coding exon 9) of the GOLGA6L10 gene. This alteration results from a G to A substitution at nucleotide position 1357, causing the glutamic acid (E) at amino acid position 453 to be replaced by a lysine (K). 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	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0092	.;.;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.56	T;T;T
M_CAP	Benign	0.00090	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.52	T
Sift4G	Uncertain	0.038	D;T;T
Vest4		0.13
MVP		0.014
ClinPred		0.74	D
Varity_R		0.083
gMVP		0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-82635213;