Variant 15-20534522-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001145004.2(GOLGA6L6):c.1912C>A(p.Gln638Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000551 in 1,522,104 control chromosomes in the GnomAD database, including 7 homozygotes. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 40)

Exomes 𝑓: 0.00055 ( 7 hom. )

Consequence

GOLGA6L6
NM_001145004.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -6.38

Variant links:

Genes affected

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

GOLGA6L6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005861342).

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGA6L6	NM_001145004.2 linkuse as main transcript	c.1912C>A	p.Gln638Lys	missense_variant	8/9	ENST00000619213.1	NP_001138476.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLGA6L6	ENST00000619213.1 linkuse as main transcript	c.1912C>A	p.Gln638Lys	missense_variant	8/9	5	NM_001145004.2	ENSP00000480376	P1

Frequencies

GnomAD3 genomes

AF:

0.000548

AC:

AN:

145860

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000263

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000679

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00330

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000674

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000590

AC:

AN:

147418

Hom.:

AF XY:

0.000484

AC XY:

AN XY:

78486

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000207

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00373

Gnomad NFE exome

AF:

0.000548

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000551

AC:

758

AN:

1376144

Hom.:

Cov.:

AF XY:

0.000514

AC XY:

349

AN XY:

679224

show subpopulations

Gnomad4 AFR exome

AF:

0.000132

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.0000408

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00288

Gnomad4 NFE exome

AF:

0.000550

Gnomad4 OTH exome

AF:

0.000459

GnomAD4 genome

AF:

0.000548

AC:

AN:

145960

Hom.:

Cov.:

AF XY:

0.000632

AC XY:

AN XY:

71240

show subpopulations

Gnomad4 AFR

AF:

0.0000262

Gnomad4 AMR

AF:

0.0000679

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00330

Gnomad4 NFE

AF:

0.000674

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000555

Hom.:

ExAC

AF:

0.000396

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.1990C>A (p.Q664K) alteration is located in exon 8 (coding exon 8) of the GOLGA6L6 gene. This alteration results from a C to A substitution at nucleotide position 1990, causing the glutamine (Q) at amino acid position 664 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.023

DANN

Benign

0.28

DEOGEN2

Benign

0.0071

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.078

MetaRNN

Benign

0.0059

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.61

Sift4G

Benign

0.38

Vest4

0.10

MVP

0.014

ClinPred

0.026

Varity_R

0.081

gMVP

0.0019

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

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