chr15-82342859-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 11/17 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
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15849277).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164465.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6L10	NM_001164465.3	MANE Select	c.1486G>A	p.Glu496Lys	missense	Exon 9 of 9	NP_001157937.2	A6NI86

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6L10	ENST00000610657.2	TSL:2 MANE Select	c.1486G>A	p.Glu496Lys	missense	Exon 9 of 9	ENSP00000479362.1	A6NI86
	GOLGA6L10	ENST00000621197.4	TSL:5	c.1237G>A	p.Glu413Lys	missense	Exon 10 of 10	ENSP00000484254.2	A0A087X1J3

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33404

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5116

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111832

Other (OTH) AF: 0.00 AC: 0 AN: 60272

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 54

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.00090	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.19
PrimateAI	Uncertain	0.52	T
Sift4G	Uncertain	0.038	D
Vest4		0.13
MVP		0.014
ClinPred		0.74	D
Varity_R		0.083
gMVP		0.10
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr15-82635213;