chr15-23129937-C-T

Variant names:

• chr15-23129937-C-T
• rs774621315
• NM_001001413.3:c.1516G>A

Variant summary

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

The NM_001001413.3(GOLGA6L1):​c.1516G>A​(p.Asp506Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.000017 (0 hom., cov: 20)
  • Exomes 𝑓: 0.000036 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L1 NM_001001413.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.08

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=0.09356475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA6L1	NM_001001413.3	c.1516G>A	p.Asp506Asn	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.1516G>A	p.Asp506Asn	missense_variant	Exon 8 of 9	5	NM_001001413.3	ENSP00000478478.1

Frequencies

GnomAD3 genomes AF: 0.0000173 AC: 2 AN: 115604 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.0000316

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: 0.0000184

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000361 AC: 20 AN: 553798 Hom.: 0 Cov.: 7 AF XY: 0.0000339 AC XY: 10 AN XY: 294698

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: 0.0000182

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000494

Gnomad4 OTH exome AF: 0.0000357

GnomAD4 genome AF: 0.0000173 AC: 2 AN: 115604 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 55570

Gnomad4 AFR AF: 0.0000316

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: 0.0000184

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000103 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 23, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1516G>A (p.D506N) 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 1516, causing the aspartic acid (D) at amino acid position 506 to be replaced by an asparagine (N). 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	0.10
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.2
DANN	Benign	0.47
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.094	T
Sift4G	Benign	0.12	T
Vest4		0.13
MVP		0.040
GERP RS		0.15
Varity_R		0.048
gMVP		0.0058

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: rs774621315; hg19: chr15-23407377;