15-20534496-C-G

Position:

• chr15-20534496-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145004.2(GOLGA6L6):​c.1938G>C​(p.Arg646Ser) 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. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GOLGA6L6 NM_001145004.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.690

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0394381).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGA6L6	NM_001145004.2	c.1938G>C	p.Arg646Ser	missense_variant	8/9	ENST00000619213.1	NP_001138476.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLGA6L6	ENST00000619213.1	c.1938G>C	p.Arg646Ser	missense_variant	8/9	5	NM_001145004.2	ENSP00000480376	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 31

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

Jun 24, 2022

The c.2016G>C (p.R672S) alteration is located in exon 8 (coding exon 8) of the GOLGA6L6 gene. This alteration results from a G to C substitution at nucleotide position 2016, causing the arginine (R) at amino acid position 672 to be replaced by a serine (S). 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	Benign	0.26
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.2
DANN	Benign	0.33
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.56	T
Sift4G	Benign	0.30	T
Vest4		0.14
MVP		0.014
ClinPred		0.13	T
Varity_R		0.12
gMVP		0.0098

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: rs1890290411; hg19: chr15-20739734;