15-20534506-G-T

Variant names:

• chr15-20534506-G-T
• rs28626390
• NM_001145004.2:c.1928C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145004.2(GOLGA6L6):​c.1928C>A​(p.Thr643Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 984,482 control chromosomes in the GnomAD database, including 955 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (16 hom., cov: 0)
  • Exomes 𝑓: 0.046 (955 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L6 NM_001145004.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03943795).
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA6L6	NM_001145004.2	c.1928C>A	p.Thr643Lys	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.1928C>A	p.Thr643Lys	missense_variant	Exon 8 of 9	5	NM_001145004.2	ENSP00000480376.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 7530 AN: 27226 Hom.: 16 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.303

GnomAD4 exome AF: 0.0459 AC: 45226 AN: 984482 Hom.: 955 Cov.: 47 AF XY: 0.0508 AC XY: 24048 AN XY: 473470

Gnomad4 AFR exome AF: 0.0664

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.0918

Gnomad4 EAS exome AF: 0.305

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.158

Gnomad4 NFE exome AF: 0.0298

Gnomad4 OTH exome AF: 0.0696

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.276 AC: 7529 AN: 27248 Hom.: 16 Cov.: 0 AF XY: 0.279 AC XY: 3850 AN XY: 13792

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.301

Alfa AF: 0.00269 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.030
DANN	Benign	0.30
DEOGEN2	Benign	0.00042	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.00014	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.99	T
PrimateAI	Uncertain	0.61	T
Sift4G	Benign	0.91	T
Vest4		0.12
MVP		0.014
ClinPred		0.030	T
Varity_R		0.072
gMVP		0.0023

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

LitVar

Other links and lift over

dbSNP: rs28626390; hg19: chr15-20739744; COSMIC: COSV71180511;