15-20534587-G-A

Variant names:

• chr15-20534587-G-A
• rs28590435
• NM_001145004.2:c.1847C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2 BP4_Strong BP6_Very_Strong BS1

The NM_001145004.2(GOLGA6L6):​c.1847C>T​(p.Thr616Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 97,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0039 (8 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L6 NM_001145004.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.18

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• PM2: Variant has high frequency in the AFR(0.00867279) population. However there is too low homozygotes in high coverage region: (expected more than 22, got 0).
• BP4: Computational evidence support a benign effect (MetaRNN=0.0030660033).
• BP6: Variant 15-20534587-G-A is Benign according to our data. Variant chr15-20534587-G-A is described in ClinVar as [Benign]. Clinvar id is 402906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0302 (2941/97252) while in subpopulation AFR AF= 0.0425 (995/23426). AF 95% confidence interval is 0.0403. There are 0 homozygotes in gnomad4. There are 1382 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA6L6	NM_001145004.2	c.1847C>T	p.Thr616Met	missense_variant	Exon 8 of 9	ENST00000619213.1	NP_001138476.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA6L6	ENST00000619213.1	c.1847C>T	p.Thr616Met	missense_variant	Exon 8 of 9	5	NM_001145004.2	ENSP00000480376.1

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 2945 AN: 97150 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0427

Gnomad AMI AF: 0.0115

Gnomad AMR AF: 0.0200

Gnomad ASJ AF: 0.0177

Gnomad EAS AF: 0.00129

Gnomad SAS AF: 0.0176

Gnomad FIN AF: 0.0295

Gnomad MID AF: 0.0362

Gnomad NFE AF: 0.0307

Gnomad OTH AF: 0.0302

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00387 AC: 4674 AN: 1208304 Hom.: 8 Cov.: 66 AF XY: 0.00376 AC XY: 2242 AN XY: 595844

Gnomad4 AFR exome AF: 0.00965

Gnomad4 AMR exome AF: 0.00350

Gnomad4 ASJ exome AF: 0.00273

Gnomad4 EAS exome AF: 0.0000883

Gnomad4 SAS exome AF: 0.00125

Gnomad4 FIN exome AF: 0.00605

Gnomad4 NFE exome AF: 0.00396

Gnomad4 OTH exome AF: 0.00430

GnomAD4 genome AF: 0.0302 AC: 2941 AN: 97252 Hom.: 0 Cov.: 34 AF XY: 0.0290 AC XY: 1382 AN XY: 47672

Gnomad4 AFR AF: 0.0425

Gnomad4 AMR AF: 0.0199

Gnomad4 ASJ AF: 0.0177

Gnomad4 EAS AF: 0.00130

Gnomad4 SAS AF: 0.0179

Gnomad4 FIN AF: 0.0295

Gnomad4 NFE AF: 0.0306

Gnomad4 OTH AF: 0.0299

Alfa AF: 0.0570 Hom.: 18

ExAC AF: 0.0675 AC: 1379

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.24
DANN	Benign	0.22
DEOGEN2	Benign	0.00060	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.00091	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.56	T
Sift4G	Benign	0.22	T
Vest4		0.035
ClinPred		0.016	T
Varity_R		0.015
gMVP		0.0038

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: rs28590435; hg19: chr15-20739825; COSMIC: COSV71180651;