chr15-82344626-C-T

Variant names:

• chr15-82344626-C-T
• rs1397222807
• NM_001164465.3:c.1234G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164465.3(GOLGA6L10):​c.1234G>A​(p.Glu412Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000675 in 148,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000068 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00081 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L10 NM_001164465.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.654
• Publications: 1 publications found

Genes affected

GOLGA6L10 (HGNC:37228): (golgin A6 family like 10)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09367889).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164465.3. 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
	GOLGA6L10	NM_001164465.3	MANE Select	c.1234G>A	p.Glu412Lys	missense	Exon 6 of 9	NP_001157937.2	A6NI86

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6L10	ENST00000610657.2	TSL:2 MANE Select	c.1234G>A	p.Glu412Lys	missense	Exon 6 of 9	ENSP00000479362.1	A6NI86
	GOLGA6L10	ENST00000621197.4	TSL:5	c.985G>A	p.Glu329Lys	missense	Exon 7 of 10	ENSP00000484254.2	A0A087X1J3

Frequencies

GnomAD3 genomes AF: 0.0000675 AC: 10 AN: 148114 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000524

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: 0.000192

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000738

Gnomad OTH AF: 0.000483

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000808 AC: 1131 AN: 1400124 Hom.: 0 Cov.: 36 AF XY: 0.000764 AC XY: 530 AN XY: 693450

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

African (AFR) AF: 0.0000960 AC: 3 AN: 31254

American (AMR) AF: 0.000221 AC: 9 AN: 40688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25420

East Asian (EAS) AF: 0.0000526 AC: 2 AN: 37990

South Asian (SAS) AF: 0.000209 AC: 17 AN: 81164

European-Finnish (FIN) AF: 0.000446 AC: 16 AN: 35892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4088

European-Non Finnish (NFE) AF: 0.000972 AC: 1055 AN: 1085150

Other (OTH) AF: 0.000496 AC: 29 AN: 58478

⚠️ 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: 0.0000675 AC: 10 AN: 148114 Hom.: 0 Cov.: 31 AF XY: 0.0000830 AC XY: 6 AN XY: 72306

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

African (AFR) AF: 0.0000524 AC: 2 AN: 38154

American (AMR) AF: 0.00 AC: 0 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.00 AC: 0 AN: 4696

European-Finnish (FIN) AF: 0.000192 AC: 2 AN: 10434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000738 AC: 5 AN: 67742

Other (OTH) AF: 0.000483 AC: 1 AN: 2070

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000908485), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

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	Benign	0.20
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.0
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.094	T
PhyloP100		-0.65
PrimateAI	Uncertain	0.78	T
Sift4G	Benign	0.65	T
Vest4		0.23
MVP		0.014
gMVP		0.069

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: rs1397222807; hg19: chr15-83013265;