NM_001395373.1:c.1493T>C

Variant names:

• chr15-23364531-T-C
• rs3826016
• NM_001395373.1:c.1493T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001395373.1(GOLGA8S):​c.1493T>C​(p.Ile498Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 1,587,840 control chromosomes in the GnomAD database, including 133 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0098 (10 hom., cov: 27)
  • Exomes 𝑓: 0.0045 (123 hom.)
• Consequence: GOLGA8S NM_001395373.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.88
• Publications: 4 publications found

Genes affected

GOLGA8S (HGNC:44409): (golgin A8 family member S) Predicted to be involved in Golgi organization. Predicted to be active in Golgi cis cisterna; Golgi cisterna membrane; and cis-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

LOC105370726 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008637726).
• BP6: Variant 15-23364531-T-C is Benign according to our data. Variant chr15-23364531-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3770700.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395373.1. 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
	GOLGA8S	NM_001395373.1	MANE Select	c.1493T>C	p.Ile498Thr	missense	Exon 17 of 19	NP_001382302.1	H3BPF8
	GOLGA8S	NM_001355465.2		c.815T>C	p.Ile272Thr	missense	Exon 16 of 18	NP_001342394.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA8S	ENST00000562295.3	TSL:5 MANE Select	c.1493T>C	p.Ile498Thr	missense	Exon 17 of 19	ENSP00000455298.2	H3BPF8
	GOLGA8S	ENST00000604046.1	TSL:1	n.1828T>C		non_coding_transcript_exon	Exon 16 of 18

Frequencies

GnomAD3 genomes AF: 0.00980 AC: 1460 AN: 149052 Hom.: 10 Cov.: 27

Gnomad AFR AF: 0.00750

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00895

Gnomad ASJ AF: 0.0111

Gnomad EAS AF: 0.00375

Gnomad SAS AF: 0.00957

Gnomad FIN AF: 0.0188

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.00781

GnomAD2 exomes AF: 0.00798 AC: 1836 AN: 229980 AF XY: 0.00788

Gnomad AFR exome AF: 0.00820

Gnomad AMR exome AF: 0.00602

Gnomad ASJ exome AF: 0.00809

Gnomad EAS exome AF: 0.00241

Gnomad FIN exome AF: 0.0130

Gnomad NFE exome AF: 0.00894

Gnomad OTH exome AF: 0.00856

GnomAD4 exome AF: 0.00452 AC: 6506 AN: 1438666 Hom.: 123 Cov.: 45 AF XY: 0.00479 AC XY: 3432 AN XY: 716062

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

African (AFR) AF: 0.00463 AC: 153 AN: 33036

American (AMR) AF: 0.00513 AC: 227 AN: 44290

Ashkenazi Jewish (ASJ) AF: 0.00863 AC: 223 AN: 25826

East Asian (EAS) AF: 0.00119 AC: 47 AN: 39656

South Asian (SAS) AF: 0.00642 AC: 548 AN: 85386

European-Finnish (FIN) AF: 0.0153 AC: 678 AN: 44268

Middle Eastern (MID) AF: 0.00183 AC: 9 AN: 4912

European-Non Finnish (NFE) AF: 0.00390 AC: 4294 AN: 1101526

Other (OTH) AF: 0.00547 AC: 327 AN: 59766

⚠️ 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: 0.00980 AC: 1462 AN: 149174 Hom.: 10 Cov.: 27 AF XY: 0.0101 AC XY: 739 AN XY: 72826

African (AFR) AF: 0.00753 AC: 303 AN: 40252

American (AMR) AF: 0.00894 AC: 134 AN: 14996

Ashkenazi Jewish (ASJ) AF: 0.0111 AC: 38 AN: 3426

East Asian (EAS) AF: 0.00376 AC: 19 AN: 5058

South Asian (SAS) AF: 0.00957 AC: 44 AN: 4600

European-Finnish (FIN) AF: 0.0188 AC: 194 AN: 10324

Middle Eastern (MID) AF: 0.00690 AC: 2 AN: 290

European-Non Finnish (NFE) AF: 0.0106 AC: 712 AN: 67250

Other (OTH) AF: 0.00773 AC: 16 AN: 2070

Alfa AF: 0.00674 Hom.: 1

ExAC AF: 0.00950 AC: 1111

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.2
DANN	Benign	0.38
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0086	T
PhyloP100		2.9
PROVEAN	Benign	-0.040	N
Sift	Benign	0.19	T
Sift4G	Benign	0.43	T
Vest4		0.17
MVP		0.55
MPC		1.8
GERP RS		0.83
Varity_R		0.025
gMVP		0.12
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3826016; hg19: chr15-23609678; COSMIC: COSV71846925; COSMIC: COSV71846925;