15-23130480-C-T

Variant names:

• chr15-23130480-C-T
• rs1370320942
• NM_001001413.3:c.973G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001001413.3(GOLGA6L1):​c.973G>A​(p.Glu325Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.00031 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L1 NM_001001413.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.64

Genes affected

GOLGA6L1 (HGNC:37444): (golgin A6 family like 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.105219424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA6L1	NM_001001413.3	c.973G>A	p.Glu325Lys	missense_variant	Exon 8 of 9	ENST00000614055.2	NP_001001413.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA6L1	ENST00000614055.2	c.973G>A	p.Glu325Lys	missense_variant	Exon 8 of 9	5	NM_001001413.3	ENSP00000478478.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000309 AC: 18 AN: 58230 Hom.: 0 Cov.: 0 AF XY: 0.000203 AC XY: 6 AN XY: 29558

Gnomad4 AFR exome AF: 0.000481

Gnomad4 AMR exome AF: 0.000295

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000525

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000350

Gnomad4 OTH exome AF: 0.000329

GnomAD4 genome Cov.: 0

Alfa AF: 0.000245 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 26, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.973G>A (p.E325K) alteration is located in exon 8 (coding exon 8) of the GOLGA6L1 gene. This alteration results from a G to A substitution at nucleotide position 973, causing the glutamic acid (E) at amino acid position 325 to be replaced by a lysine (K). 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	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.58
FATHMM_MKL	Benign	0.00038	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.11	T
PrimateAI	Uncertain	0.56	T
Sift4G	Benign	0.11	T
Vest4		0.13
MVP		0.030
GERP RS		-0.61
Varity_R		0.056
gMVP		0.020

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: rs1370320942; hg19: chr15-23407881;