15-82344842-A-C

Variant names:

• chr15-82344842-A-C
• rs770136125
• NM_001164465.3:c.1018T>G

Variant summary

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

The NM_001164465.3(GOLGA6L10):​c.1018T>G​(p.Leu340Val) 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L10 NM_001164465.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.66

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=0.07977727).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA6L10	NM_001164465.3	c.1018T>G	p.Leu340Val	missense_variant	Exon 6 of 9	ENST00000610657.2	NP_001157937.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA6L10	ENST00000610657.2	c.1018T>G	p.Leu340Val	missense_variant	Exon 6 of 9	2	NM_001164465.3	ENSP00000479362.1
GOLGA6L10	ENST00000621197.4	c.769T>G	p.Leu257Val	missense_variant	Exon 7 of 10	5		ENSP00000484254.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1382720 Hom.: 0 Cov.: 46 AF XY: 0.00 AC XY: 0 AN XY: 682668

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.000637 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.949C>G (p.L317V) alteration is located in exon 6 (coding exon 6) of the GOLGA6L10 gene. This alteration results from a C to G substitution at nucleotide position 949, causing the leucine (L) at amino acid position 317 to be replaced by a valine (V). 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	0.20
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.1
DANN	Benign	0.30
DEOGEN2	Benign	0.025	.;.;T
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.39	T;T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.080	T;T;T
PrimateAI	Benign	0.45	T
Sift4G	Benign	0.66	T;T;T
Vest4		0.10
MVP		0.030
Varity_R		0.036
gMVP		0.012

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: rs770136125; hg19: chr15-83013481;