X-106033560-C-T

Variant names:

• chrX-106033560-C-T
• rs1057524273
• NM_000354.6:c.1188G>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000354.6(SERPINA7):​c.1188G>A​(p.Leu396Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: SERPINA7 NM_000354.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=-0.043 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA7	NM_000354.6	c.1188G>A	p.Leu396Leu	synonymous_variant	Exon 5 of 5	ENST00000372563.2	NP_000345.2
SERPINA7	XM_006724683.3	c.1218G>A	p.Leu406Leu	synonymous_variant	Exon 5 of 5		XP_006724746.1
SERPINA7	XM_005262180.5	c.*133G>A		3_prime_UTR_variant	Exon 5 of 5		XP_005262237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA7	ENST00000372563.2	c.1188G>A	p.Leu396Leu	synonymous_variant	Exon 5 of 5	5	NM_000354.6	ENSP00000361644.1
SERPINA7	ENST00000327674.8	c.1188G>A	p.Leu396Leu	synonymous_variant	Exon 4 of 4	1		ENSP00000329374.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.6
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1057524273; hg19: chrX-105277551;