chr15-20534482-A-G

Position:

• chr15-20534482-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145004.2(GOLGA6L6):​c.1952T>C​(p.Ile651Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000347 in 138,350 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (1 hom., cov: 30)
  • Exomes 𝑓: 0.000030 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L6 NM_001145004.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023920089).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GOLGA6L6	NM_001145004.2	c.1952T>C	p.Ile651Thr	missense_variant	8/9	ENST00000619213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOLGA6L6	ENST00000619213.1	c.1952T>C	p.Ile651Thr	missense_variant	8/9	5	NM_001145004.2	P1

Frequencies

GnomAD3 genomes AF: 0.000333 AC: 46 AN: 138250 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00130

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: 0.0000154

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000295 AC: 39 AN: 1319796 Hom.: 0 Cov.: 37 AF XY: 0.0000323 AC XY: 21 AN XY: 650458

Gnomad4 AFR exome AF: 0.000395

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000252

Gnomad4 OTH exome AF: 0.0000372

GnomAD4 genome AF: 0.000347 AC: 48 AN: 138350 Hom.: 1 Cov.: 30 AF XY: 0.000327 AC XY: 22 AN XY: 67332

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000154

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000422 Hom.: 0

ExAC AF: 0.0000809 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 07, 2022

The c.2030T>C (p.I677T) alteration is located in exon 8 (coding exon 8) of the GOLGA6L6 gene. This alteration results from a T to C substitution at nucleotide position 2030, causing the isoleucine (I) at amino acid position 677 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.5
DANN	Benign	0.24
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.65	T
Sift4G	Benign	0.071	T
Vest4		0.24
MVP		0.014
ClinPred		0.018	T
Varity_R		0.042
gMVP		0.0028

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: rs754228705; hg19: chr15-20739720;