15-23129898-A-G

Variant names:

• chr15-23129898-A-G
• rs1374626047
• NM_001001413.3:c.1555T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001001413.3(GOLGA6L1):​c.1555T>C​(p.Trp519Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 6/7 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L1 NM_001001413.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.92
• Publications: 3 publications found

Genes affected

GOLGA6L1 (HGNC:37444): (golgin A6 family like 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06880534).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001413.3. 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
	GOLGA6L1	NM_001001413.3	MANE Select	c.1555T>C	p.Trp519Arg	missense	Exon 8 of 9	NP_001001413.3	Q8N7Z2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6L1	ENST00000614055.2	TSL:5 MANE Select	c.1555T>C	p.Trp519Arg	missense	Exon 8 of 9	ENSP00000478478.1	Q8N7Z2

Frequencies

GnomAD3 genomes AF: 0.00148 AC: 166 AN: 112030 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00168

Gnomad AMR AF: 0.00129

Gnomad ASJ AF: 0.00108

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.00193

Gnomad FIN AF: 0.00204

Gnomad MID AF: 0.00658

Gnomad NFE AF: 0.00144

Gnomad OTH AF: 0.00131

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000240 AC: 181 AN: 753020 Hom.: 0 Cov.: 19 AF XY: 0.000285 AC XY: 111 AN XY: 389850

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

African (AFR) AF: 0.0000466 AC: 1 AN: 21462

American (AMR) AF: 0.000458 AC: 14 AN: 30558

Ashkenazi Jewish (ASJ) AF: 0.000102 AC: 2 AN: 19566

East Asian (EAS) AF: 0.00152 AC: 44 AN: 29034

South Asian (SAS) AF: 0.000449 AC: 27 AN: 60120

European-Finnish (FIN) AF: 0.0000451 AC: 2 AN: 44360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3550

European-Non Finnish (NFE) AF: 0.000161 AC: 82 AN: 509138

Other (OTH) AF: 0.000255 AC: 9 AN: 35232

⚠️ 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: 0.00147 AC: 165 AN: 112184 Hom.: 0 Cov.: 34 AF XY: 0.00151 AC XY: 83 AN XY: 54966

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

African (AFR) AF: 0.00144 AC: 45 AN: 31164

American (AMR) AF: 0.00129 AC: 15 AN: 11606

Ashkenazi Jewish (ASJ) AF: 0.00108 AC: 3 AN: 2778

East Asian (EAS) AF: 0.00155 AC: 5 AN: 3222

South Asian (SAS) AF: 0.00160 AC: 5 AN: 3122

European-Finnish (FIN) AF: 0.00204 AC: 15 AN: 7356

Middle Eastern (MID) AF: 0.00641 AC: 1 AN: 156

European-Non Finnish (NFE) AF: 0.00144 AC: 73 AN: 50636

Other (OTH) AF: 0.00129 AC: 2 AN: 1548

⚠️ 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: 0.000421 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
CADD	Benign	5.4
DANN	Benign	0.32
LIST_S2	Benign	0.021	T
MetaRNN	Benign	0.069	T
PhyloP100		-2.9
Sift4G	Benign	0.41	T
Vest4		0.11
gMVP		0.015

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: rs1374626047;