15-82344845-G-T

Position:

• chr15-82344845-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164465.3(GOLGA6L10):​c.1015C>A​(p.Leu339Met) 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. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L10 NM_001164465.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.60

Genes affected

GOLGA6L10 (HGNC:37228): (golgin A6 family like 10)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0920217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGA6L10	NM_001164465.3	c.1015C>A	p.Leu339Met	missense_variant	6/9	ENST00000610657.2	NP_001157937.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLGA6L10	ENST00000610657.2	c.1015C>A	p.Leu339Met	missense_variant	6/9	2	NM_001164465.3	ENSP00000479362.1
GOLGA6L10	ENST00000621197.4	c.766C>A	p.Leu256Met	missense_variant	7/10	5		ENSP00000484254.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000145 AC: 2 AN: 1382894 Hom.: 0 Cov.: 46 AF XY: 0.00000146 AC XY: 1 AN XY: 682750

Gnomad4 AFR exome AF: 0.00

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: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Dec 19, 2022

The c.946C>A (p.L316I) alteration is located in exon 6 (coding exon 6) of the GOLGA6L10 gene. This alteration results from a C to A substitution at nucleotide position 946, causing the leucine (L) at amino acid position 316 to be replaced by an isoleucine (I). 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	0.25
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.4
DANN	Benign	0.58
DEOGEN2	Benign	0.0072	.;.;T
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.31	T;T;T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.092	T;T;T
PrimateAI	Benign	0.44	T
Sift4G	Benign	0.28	T;T;T
Vest4		0.17
MVP		0.014
Varity_R		0.073
gMVP		0.024

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: rs1284363730; hg19: chr15-83013484;