chr15-23443797-A-C

Variant names:

• chr15-23443797-A-C
• rs4778531
• NM_001304388.2:c.571T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001304388.2(GOLGA6L2):​c.571T>G​(p.Trp191Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,386,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: GOLGA6L2 NM_001304388.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 11 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07800135).

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.571T>G	p.Trp191Gly	missense	Exon 5 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.571T>G	p.Trp191Gly	missense	Exon 5 of 8	ENSP00000454407.1	Q8N9W4-3
	GOLGA6L2	ENST00000566571.5	TSL:5	n.541T>G		non_coding_transcript_exon	Exon 4 of 7	ENSP00000456523.1	H3BS38

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1386514 Hom.: 0 Cov.: 44 AF XY: 0.00000146 AC XY: 1 AN XY: 684400

⚠️ 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: 31662

American (AMR) AF: 0.00 AC: 0 AN: 35984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.0000279 AC: 1 AN: 35888

South Asian (SAS) AF: 0.00 AC: 0 AN: 79342

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080366

Other (OTH) AF: 0.00 AC: 0 AN: 58156

⚠️ 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 Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.78
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.13
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.039
Sift4G	Benign	0.25	T
Polyphen		0.020	B
Vest4		0.13
MutPred		0.50		Gain of disorder (P = 0.004)
MVP		0.030
MPC		0.015
ClinPred		0.033	T
Varity_R		0.13
gMVP		0.046
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs4778531; hg19: chr15-23688944;