rs754228705

Variant names:

• chr15-20534482-A-G
• rs754228705
• NM_001145004.2:c.1952T>C

Variant summary

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

The NM_001145004.2(GOLGA6L6):​c.1952T>C​(p.Ile651Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000347 in 138,350 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (1 hom., cov: 30)
  • Exomes 𝑓: 0.000030 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L6 NM_001145004.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03
• Publications: 0 publications found

Genes affected

GOLGA6L6 (HGNC:37225): (golgin A6 family like 6)

ENSG00000294965 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.023920089).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145004.2. 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
	GOLGA6L6	NM_001145004.2	MANE Select	c.1952T>C	p.Ile651Thr	missense	Exon 8 of 9	NP_001138476.2	A8MZA4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6L6	ENST00000619213.1	TSL:5 MANE Select	c.1952T>C	p.Ile651Thr	missense	Exon 8 of 9	ENSP00000480376.1	A8MZA4
	ENSG00000294965	ENST00000727099.1		n.182+3829A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000333 AC: 46 AN: 138250 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00130

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: 0.0000154

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000546 AC: 8 AN: 146574 AF XY: 0.0000256

Gnomad AFR exome AF: 0.000995

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: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000295 AC: 39 AN: 1319796 Hom.: 0 Cov.: 37 AF XY: 0.0000323 AC XY: 21 AN XY: 650458

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

African (AFR) AF: 0.000395 AC: 11 AN: 27880

American (AMR) AF: 0.00 AC: 0 AN: 30588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23100

East Asian (EAS) AF: 0.00 AC: 0 AN: 30558

South Asian (SAS) AF: 0.00 AC: 0 AN: 72246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4272

European-Non Finnish (NFE) AF: 0.0000252 AC: 26 AN: 1032810

Other (OTH) AF: 0.0000372 AC: 2 AN: 53784

⚠️ 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 AF: 0.000347 AC: 48 AN: 138350 Hom.: 1 Cov.: 30 AF XY: 0.000327 AC XY: 22 AN XY: 67332

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

African (AFR) AF: 0.00135 AC: 47 AN: 34742

American (AMR) AF: 0.00 AC: 0 AN: 13858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3376

East Asian (EAS) AF: 0.00 AC: 0 AN: 4858

South Asian (SAS) AF: 0.00 AC: 0 AN: 4328

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 248

European-Non Finnish (NFE) AF: 0.0000154 AC: 1 AN: 64932

Other (OTH) AF: 0.00 AC: 0 AN: 1964

⚠️ 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: 0.000422 Hom.: 0

ExAC AF: 0.0000809 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	Uncertain	0.47
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.5
DANN	Benign	0.24
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.93	T
PhyloP100		1.0
PrimateAI	Uncertain	0.65	T
Sift4G	Benign	0.071	T
Vest4		0.24
MVP		0.014
ClinPred		0.018	T
Varity_R		0.042
gMVP		0.0028
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: rs754228705; hg19: chr15-20739720;