Genetic Variant GOLGA6L4:p.Asp412Asp (chr15-84240590-T-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001267536.3(GOLGA6L4):c.1236T>C(p.Asp412Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 6)

Exomes 𝑓: 0.038 ( 12229 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA6L4
NM_001267536.3 synonymous

Scores

Splicing: ADA: 0.000009866

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.00

Variant links:

Genes affected

GOLGA6L4 (HGNC:27256): (golgin A6 family like 4)

GOLGA6L4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BP6

Variant 15-84240590-T-C is Benign according to our data. Variant chr15-84240590-T-C is described in ClinVar as [Benign]. Clinvar id is 1300000.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-84240590-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
GOLGA6L4	NM_001267536.3 link	c.1236T>C	p.Asp412Asp	synonymous_variant	Exon 6 of 9	ENST00000510439.7	NP_001254465.2
GOLGA6L4	XM_017022481.2 link	c.1080T>C	p.Asp360Asp	synonymous_variant	Exon 7 of 10		XP_016877970.1
GOLGA6L4	XM_017022482.2 link	c.1080T>C	p.Asp360Asp	synonymous_variant	Exon 7 of 10		XP_016877971.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GOLGA6L4	ENST00000510439.7 link	c.1236T>C	p.Asp412Asp	synonymous_variant	Exon 6 of 9	5	NM_001267536.3	ENSP00000421586.2	A6NEF3
GOLGA6L4	ENST00000512109.1 link	c.349+1185T>C		intron_variant	Intron 4 of 5	3		ENSP00000426395.1	H0YA86
GOLGA6L4	ENST00000515814.1 link	n.2291T>C		non_coding_transcript_exon_variant	Exon 2 of 2	3
GOLGA6L4	ENST00000379674.4 link	n.-27T>C		upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

66726

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000312

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000776

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00152

Gnomad SAS

AF:

0.000408

Gnomad FIN

AF:

0.000299

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000827

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0348

AC:

2861

AN:

82158

Hom.:

1326

AF XY:

0.0305

AC XY:

1381

AN XY:

45280

show subpopulations

Gnomad AFR exome

AF:

0.0563

Gnomad AMR exome

AF:

0.118

Gnomad ASJ exome

AF:

0.0121

Gnomad EAS exome

AF:

0.0120

Gnomad SAS exome

AF:

0.0111

Gnomad FIN exome

AF:

0.0212

Gnomad NFE exome

AF:

0.0243

Gnomad OTH exome

AF:

0.0415

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0382

AC:

25457

AN:

666340

Hom.:

12229

Cov.:

AF XY:

0.0383

AC XY:

12786

AN XY:

333898

show subpopulations

Gnomad4 AFR exome

AF:

0.0324

Gnomad4 AMR exome

AF:

0.135

Gnomad4 ASJ exome

AF:

0.0613

Gnomad4 EAS exome

AF:

0.0231

Gnomad4 SAS exome

AF:

0.0378

Gnomad4 FIN exome

AF:

0.0836

Gnomad4 NFE exome

AF:

0.0338

Gnomad4 OTH exome

AF:

0.0442

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000314

AC:

AN:

66848

Hom.:

Cov.:

AF XY:

0.000368

AC XY:

AN XY:

32652

show subpopulations

Gnomad4 AFR

AF:

0.000350

Gnomad4 AMR

AF:

0.000776

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00122

Gnomad4 SAS

AF:

0.000406

Gnomad4 FIN

AF:

0.000299

Gnomad4 NFE

AF:

0.0000827

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.298

Hom.:

730

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.8

DANN

Benign

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000099

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over