X-106033675-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000354.6(SERPINA7):c.1073G>A(p.Gly358Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: SERPINA7 NM_000354.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.36

Genes affected

SERPINA7 (HGNC:11583): (serpin family A member 7) There are three proteins including thyroxine-binding globulin (TBG), transthyretin and albumin responsible for carrying the thyroid hormones thyroxine (T4) and 3,5,3'-triiodothyronine (T3) in the bloodstream. This gene encodes the major thyroid hormone transport protein, TBG, in serum. It belongs to the serpin family in genomics, but the protein has no inhibitory function like many other members of the serpin family. Mutations in this gene result in TGB deficiency, which has been classified as partial deficiency, complete deficiency, and excess, based on the level of serum TBG. Alternatively spliced transcript variants encoding different isoforms have been found, but the full-length nature of these variants has not been determined.[provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINA7	NM_000354.6	c.1073G>A	p.Gly358Asp	missense_variant	5/5	ENST00000372563.2
SERPINA7	XM_006724683.3	c.1103G>A	p.Gly368Asp	missense_variant	5/5
SERPINA7	XM_005262180.5	c.*18G>A		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA7	ENST00000372563.2	c.1073G>A	p.Gly358Asp	missense_variant	5/5	5	NM_000354.6	P1
SERPINA7	ENST00000327674.8	c.1073G>A	p.Gly358Asp	missense_variant	4/4	1		P1
SERPINA7	ENST00000487487.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

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

Aug 08, 2022

The c.1073G>A (p.G358D) alteration is located in exon 5 (coding exon 4) of the SERPINA7 gene. This alteration results from a G to A substitution at nucleotide position 1073, causing the glycine (G) at amino acid position 358 to be replaced by an aspartic acid (D). 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	Benign	0.10
BayesDel_addAF	Benign	-0.0062	T
BayesDel_noAF	Benign	-0.25
Cadd	Benign	14
Dann	Uncertain	0.99
DEOGEN2	Benign	0.024	T;T
FATHMM_MKL	Benign	0.58	D
M_CAP	Pathogenic	0.48	D
MetaRNN	Uncertain	0.50	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.22	N;N
MutationTaster	Benign	0.91	D;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.67	N;N
REVEL	Uncertain	0.37
Sift	Benign	0.37	T;T
Sift4G	Benign	0.70	T;T
Polyphen		0.69	P;P
Vest4		0.15
MutPred		0.50		Gain of catalytic residue at G358 (P = 0.0342);Gain of catalytic residue at G358 (P = 0.0342);
MVP		1.0
MPC		0.089
ClinPred		0.80	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.45

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: chrX-105277666;