rs368864824

Variant names:

• chr15-23440500-C-T
• rs368864824
• NM_001304388.2:c.1975G>A

Variant summary

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

The NM_001304388.2(GOLGA6L2):​c.1975G>A​(p.Glu659Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 0)
  • Exomes 𝑓: 0.015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L2 NM_001304388.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.432
• Publications: 6 publications found

Genes affected

GOLGA6L2 (HGNC:26695): (golgin A6 family like 2) Predicted to be located in cis-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0054126084).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304388.2. 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
	GOLGA6L2	NM_001304388.2	MANE Select	c.1975G>A	p.Glu659Lys	missense	Exon 8 of 8	NP_001291317.1	Q8N9W4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6L2	ENST00000567107.6	TSL:5 MANE Select	c.1975G>A	p.Glu659Lys	missense	Exon 8 of 8	ENSP00000454407.1	Q8N9W4-3
	GOLGA6L2	ENST00000566571.5	TSL:5	n.*1256G>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000456523.1	H3BS38
	GOLGA6L2	ENST00000566571.5	TSL:5	n.*1256G>A		3_prime_UTR	Exon 7 of 7	ENSP00000456523.1	H3BS38

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 16 AN: 13778 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000841

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.0229

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000768

Gnomad OTH AF: 0.00758

GnomAD2 exomes AF: 0.000580 AC: 15 AN: 25850 AF XY: 0.000382

Gnomad AFR exome AF: 0.00157

Gnomad AMR exome AF: 0.000509

Gnomad ASJ exome AF: 0.00111

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00196

Gnomad NFE exome AF: 0.000411

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0150 AC: 1797 AN: 120004 Hom.: 0 Cov.: 0 AF XY: 0.0140 AC XY: 861 AN XY: 61710

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

African (AFR) AF: 0.00397 AC: 23 AN: 5798

American (AMR) AF: 0.00134 AC: 6 AN: 4472

Ashkenazi Jewish (ASJ) AF: 0.00779 AC: 19 AN: 2438

East Asian (EAS) AF: 0.00206 AC: 8 AN: 3882

South Asian (SAS) AF: 0.00405 AC: 44 AN: 10856

European-Finnish (FIN) AF: 0.00163 AC: 8 AN: 4922

Middle Eastern (MID) AF: 0.0202 AC: 8 AN: 396

European-Non Finnish (NFE) AF: 0.0198 AC: 1616 AN: 81634

Other (OTH) AF: 0.0116 AC: 65 AN: 5606

⚠️ 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: 0.00116 AC: 16 AN: 13804 Hom.: 0 Cov.: 0 AF XY: 0.000891 AC XY: 6 AN XY: 6732

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

African (AFR) AF: 0.000837 AC: 6 AN: 7170

American (AMR) AF: 0.00 AC: 0 AN: 976

Ashkenazi Jewish (ASJ) AF: 0.0229 AC: 6 AN: 262

East Asian (EAS) AF: 0.00 AC: 0 AN: 340

South Asian (SAS) AF: 0.00 AC: 0 AN: 394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 12

European-Non Finnish (NFE) AF: 0.000768 AC: 3 AN: 3904

Other (OTH) AF: 0.00758 AC: 1 AN: 132

⚠️ 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: 0.415 Hom.: 0

ExAC AF: 0.0000819 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.89
FATHMM_MKL	Benign	0.00095	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.0054	T
PhyloP100		0.43
PROVEAN	Benign	-0.32	N
Sift4G	Benign	0.33	T
Vest4		0.14
MVP		0.030
MPC		0.014
Varity_R		0.20
gMVP		0.065
Mutation Taster		=99/1	polymorphism

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: rs368864824; hg19: chr15-23685647; COSMIC: COSV61477081;