chr15-20534450-C-T

Variant names:

• chr15-20534450-C-T
• rs1380404004
• NM_001145004.2:c.1984G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145004.2(GOLGA6L6):​c.1984G>A​(p.Glu662Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000422 in 135,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00042 (0 hom., cov: 24)
  • Exomes 𝑓: 0.00020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L6 NM_001145004.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.30
• Publications: 0 publications found

Genes affected

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

ENSG00000294965 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06514943).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145004.2. 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
	GOLGA6L6	NM_001145004.2	MANE Select	c.1984G>A	p.Glu662Lys	missense	Exon 8 of 9	NP_001138476.2	A8MZA4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6L6	ENST00000619213.1	TSL:5 MANE Select	c.1984G>A	p.Glu662Lys	missense	Exon 8 of 9	ENSP00000480376.1	A8MZA4
	ENSG00000294965	ENST00000727099.1		n.182+3797C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000422 AC: 57 AN: 135084 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000861

Gnomad AMI AF: 0.00134

Gnomad AMR AF: 0.000367

Gnomad ASJ AF: 0.000311

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00122

Gnomad FIN AF: 0.000317

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000596

Gnomad OTH AF: 0.00108

GnomAD2 exomes AF: 0.00000703 AC: 1 AN: 142178 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000200 AC: 260 AN: 1298832 Hom.: 0 Cov.: 33 AF XY: 0.000189 AC XY: 121 AN XY: 641116

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

African (AFR) AF: 0.000109 AC: 3 AN: 27640

American (AMR) AF: 0.000587 AC: 18 AN: 30674

Ashkenazi Jewish (ASJ) AF: 0.000607 AC: 14 AN: 23070

East Asian (EAS) AF: 0.0000652 AC: 2 AN: 30698

South Asian (SAS) AF: 0.000362 AC: 26 AN: 71824

European-Finnish (FIN) AF: 0.000617 AC: 26 AN: 42170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4062

European-Non Finnish (NFE) AF: 0.000147 AC: 149 AN: 1015454

Other (OTH) AF: 0.000413 AC: 22 AN: 53240

⚠️ 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 AF: 0.000422 AC: 57 AN: 135190 Hom.: 0 Cov.: 24 AF XY: 0.000378 AC XY: 25 AN XY: 66064

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

African (AFR) AF: 0.0000858 AC: 3 AN: 34966

American (AMR) AF: 0.000367 AC: 5 AN: 13632

Ashkenazi Jewish (ASJ) AF: 0.000311 AC: 1 AN: 3218

East Asian (EAS) AF: 0.00 AC: 0 AN: 4826

South Asian (SAS) AF: 0.00122 AC: 5 AN: 4114

European-Finnish (FIN) AF: 0.000317 AC: 3 AN: 9472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 244

European-Non Finnish (NFE) AF: 0.000596 AC: 37 AN: 62090

Other (OTH) AF: 0.00106 AC: 2 AN: 1882

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000337 Hom.: 0

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	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.48
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0085	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.98	T
PhyloP100		-2.3
PrimateAI	Uncertain	0.61	T
Sift4G	Benign	0.28	T
Vest4		0.12
MVP		0.030
ClinPred		0.20	T
Varity_R		0.032
gMVP		0.013
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

dbSNP: rs1380404004; hg19: chr15-20739688;