8-41497647-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001002296.2(GOLGA7):c.250A>T(p.Thr84Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GOLGA7 NM_001002296.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32

Genes affected

GOLGA7 (HGNC:24876): (golgin A7) Involved in Golgi to plasma membrane protein transport; peptidyl-L-cysteine S-palmitoylation; and protein stabilization. Acts upstream of or within Golgi to plasma membrane transport. Located in Golgi membrane and Golgi stack. Is intrinsic component of Golgi membrane. Part of palmitoyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.759

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GOLGA7	NM_001002296.2	c.250A>T	p.Thr84Ser	missense_variant	2/5	ENST00000357743.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOLGA7	ENST00000357743.9	c.250A>T	p.Thr84Ser	missense_variant	2/5	1	NM_001002296.2	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 22

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 09, 2024

The c.250A>T (p.T84S) alteration is located in exon 2 (coding exon 2) of the GOLGA7 gene. This alteration results from a A to T substitution at nucleotide position 250, causing the threonine (T) at amino acid position 84 to be replaced by a serine (S). 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	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T;.;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	1.0	D
M_CAP	Benign	0.010	T
MetaRNN	Pathogenic	0.76	D;D;D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	2.0	M;M;M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-4.0	D;D;D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0080	D;D;T;D
Sift4G	Benign	0.12	T;T;T;T
Polyphen		1.0	D;D;.;D
Vest4		0.75
MutPred		0.74		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.44
MPC		1.8
ClinPred		0.99	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.42
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-41355166;