15-20534651-T-G

Variant names:

• chr15-20534651-T-G
• rs1291033117
• NM_001145004.2:c.1783A>C

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.1783A>C​(p.Ile595Leu) 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. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 29)
• Consequence: GOLGA6L6 NM_001145004.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 1 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=0.060125858).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA6L6	NM_001145004.2	c.1783A>C	p.Ile595Leu	missense_variant	Exon 8 of 9	ENST00000619213.1	NP_001138476.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA6L6	ENST00000619213.1	c.1783A>C	p.Ile595Leu	missense_variant	Exon 8 of 9	5	NM_001145004.2	ENSP00000480376.1
ENSG00000294965	ENST00000727099.1	n.182+3998T>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.0000151 AC: 2 AN: 132436 AF XY: 0.0000281

Gnomad AFR exome AF: 0.000290

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.4
DANN	Benign	0.43
DEOGEN2	Benign	0.00076	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00028	N
LIST_S2	Benign	0.10	T
M_CAP	Benign	0.00097	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.90	T
PhyloP100		-1.8
PrimateAI	Uncertain	0.58	T
Sift4G	Benign	1.0	T
Vest4		0.13
MVP		0.014
ClinPred		0.0086	T
Varity_R		0.10
gMVP		0.0014

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: rs1291033117; hg19: chr15-20739889;