15-20534471-C-T

Variant names:

• chr15-20534471-C-T
• rs766747148
• NM_001145004.2:c.1963G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145004.2(GOLGA6L6):​c.1963G>A​(p.Glu655Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000247 in 1,459,576 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 0.0000070 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: GOLGA6L6 NM_001145004.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.48
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0660153).

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.1963G>A	p.Glu655Lys	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.1963G>A	p.Glu655Lys	missense	Exon 8 of 9	ENSP00000480376.1	A8MZA4
	ENSG00000294965	ENST00000727099.1		n.182+3818C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000701 AC: 1 AN: 142574 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

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: 0.0000152

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000138 AC: 2 AN: 144954 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: 0.0000924

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000266 AC: 35 AN: 1317002 Hom.: 0 Cov.: 35 AF XY: 0.0000200 AC XY: 13 AN XY: 649316

African (AFR) AF: 0.0000359 AC: 1 AN: 27850

American (AMR) AF: 0.00 AC: 0 AN: 30662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23076

East Asian (EAS) AF: 0.0000328 AC: 1 AN: 30504

South Asian (SAS) AF: 0.00 AC: 0 AN: 72304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4232

European-Non Finnish (NFE) AF: 0.0000301 AC: 31 AN: 1030532

Other (OTH) AF: 0.0000372 AC: 2 AN: 53696

GnomAD4 genome AF: 0.00000701 AC: 1 AN: 142574 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 69576

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

African (AFR) AF: 0.00 AC: 0 AN: 36432

American (AMR) AF: 0.00 AC: 0 AN: 14346

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3394

East Asian (EAS) AF: 0.00 AC: 0 AN: 5026

South Asian (SAS) AF: 0.00 AC: 0 AN: 4460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000152 AC: 1 AN: 65834

Other (OTH) AF: 0.00 AC: 0 AN: 1972

⚠️ 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: 0.00 Hom.: 0

ExAC AF: 0.0000417 AC: 1

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	0.15
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.3
DANN	Benign	0.48
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00080	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.98	T
PhyloP100		-4.5
PrimateAI	Uncertain	0.61	T
Sift4G	Benign	0.78	T
Vest4		0.10
MVP		0.030
ClinPred		0.096	T
Varity_R		0.026
gMVP		0.021
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: rs766747148; hg19: chr15-20739709; COSMIC: COSV71180779;