15-23129586-A-G

Variant names:

• chr15-23129586-A-G
• rs1205365622
• NM_001001413.3:c.1867T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001001413.3(GOLGA6L1):​c.1867T>C​(p.Cys623Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000093 (0 hom., cov: 18)
  • Exomes 𝑓: 0.00012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L1 NM_001001413.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.88
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0070243776).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001413.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6L1	NM_001001413.3	MANE Select	c.1867T>C	p.Cys623Arg	missense	Exon 8 of 9	NP_001001413.3	Q8N7Z2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6L1	ENST00000614055.2	TSL:5 MANE Select	c.1867T>C	p.Cys623Arg	missense	Exon 8 of 9	ENSP00000478478.1	Q8N7Z2

Frequencies

GnomAD3 genomes AF: 0.0000935 AC: 11 AN: 117674 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000847

Gnomad ASJ AF: 0.00268

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000185

Gnomad OTH AF: 0.000656

GnomAD2 exomes AF: 0.0000725 AC: 7 AN: 96594 AF XY: 0.0000382

Gnomad AFR exome AF: 0.00120

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000259

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000124 AC: 57 AN: 457878 Hom.: 0 Cov.: 0 AF XY: 0.000132 AC XY: 32 AN XY: 243036

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 12704

American (AMR) AF: 0.00 AC: 0 AN: 20696

Ashkenazi Jewish (ASJ) AF: 0.00272 AC: 38 AN: 13950

East Asian (EAS) AF: 0.00 AC: 0 AN: 31150

South Asian (SAS) AF: 0.00 AC: 0 AN: 46054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2006

European-Non Finnish (NFE) AF: 0.0000437 AC: 12 AN: 274724

Other (OTH) AF: 0.000265 AC: 7 AN: 26412

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000935 AC: 11 AN: 117674 Hom.: 0 Cov.: 18 AF XY: 0.0000882 AC XY: 5 AN XY: 56702

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32488

American (AMR) AF: 0.0000847 AC: 1 AN: 11802

Ashkenazi Jewish (ASJ) AF: 0.00268 AC: 8 AN: 2980

East Asian (EAS) AF: 0.00 AC: 0 AN: 3222

South Asian (SAS) AF: 0.00 AC: 0 AN: 2798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7802

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 208

European-Non Finnish (NFE) AF: 0.0000185 AC: 1 AN: 54174

Other (OTH) AF: 0.000656 AC: 1 AN: 1524

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000253 Hom.: 0

ExAC AF: 0.000137 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.41
DANN	Benign	0.21
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.0070	T
PhyloP100		-1.9
Sift4G	Benign	0.56	T
Vest4		0.046
MVP		0.21
Varity_R		0.18
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

Other links and lift over

dbSNP: rs1205365622; hg19: chr15-23406387;