NM_001304388.2:c.1997A>G

Variant names:

• chr15-23440478-T-C
• rs372736971
• NM_001304388.2:c.1997A>G

Variant summary

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

The NM_001304388.2(GOLGA6L2):​c.1997A>G​(p.Glu666Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L2 NM_001304388.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.488
• Publications: 8 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0062844455).

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.1997A>G	p.Glu666Gly	missense	Exon 8 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.1997A>G	p.Glu666Gly	missense	Exon 8 of 8	ENSP00000454407.1	Q8N9W4-3
	GOLGA6L2	ENST00000566571.5	TSL:5	n.*1278A>G		non_coding_transcript_exon	Exon 7 of 7	ENSP00000456523.1	H3BS38
	GOLGA6L2	ENST00000566571.5	TSL:5	n.*1278A>G		3_prime_UTR	Exon 7 of 7	ENSP00000456523.1	H3BS38

Frequencies

GnomAD3 genomes AF: 0.000651 AC: 13 AN: 19954 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000821

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000308

Gnomad OTH AF: 0.00420

GnomAD2 exomes AF: 0.00 AC: 0 AN: 87388 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000135 AC: 28 AN: 207598 Hom.: 0 Cov.: 0 AF XY: 0.000172 AC XY: 18 AN XY: 104518

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

African (AFR) AF: 0.000145 AC: 1 AN: 6918

American (AMR) AF: 0.000188 AC: 1 AN: 5322

Ashkenazi Jewish (ASJ) AF: 0.00176 AC: 6 AN: 3402

East Asian (EAS) AF: 0.00 AC: 0 AN: 4690

South Asian (SAS) AF: 0.000221 AC: 3 AN: 13586

European-Finnish (FIN) AF: 0.000154 AC: 1 AN: 6494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 608

European-Non Finnish (NFE) AF: 0.0000886 AC: 14 AN: 157938

Other (OTH) AF: 0.000231 AC: 2 AN: 8640

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.000651 AC: 13 AN: 19982 Hom.: 0 Cov.: 0 AF XY: 0.000407 AC XY: 4 AN XY: 9832

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

African (AFR) AF: 0.000234 AC: 2 AN: 8562

American (AMR) AF: 0.00 AC: 0 AN: 1826

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 7 AN: 352

East Asian (EAS) AF: 0.00 AC: 0 AN: 572

South Asian (SAS) AF: 0.00 AC: 0 AN: 538

European-Finnish (FIN) AF: 0.000821 AC: 1 AN: 1218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 42

European-Non Finnish (NFE) AF: 0.000308 AC: 2 AN: 6496

Other (OTH) AF: 0.00417 AC: 1 AN: 240

⚠️ 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: 0.348 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.90
FATHMM_MKL	Benign	0.00067	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.0063	T
PhyloP100		-0.49
PROVEAN	Benign	-0.63	N
Sift4G	Benign	0.50	T
Vest4		0.12
MVP		0.030
MPC		0.014
Varity_R		0.073
gMVP		0.032
Mutation Taster		=100/0	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: rs372736971; hg19: chr15-23685625; COSMIC: COSV61481438;