rs1197067490

Variant names:

• chrX-106033545-C-A
• rs1197067490
• NM_000354.6:c.1203G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-106033545-C-A
• chrX-106033545-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000354.6(SERPINA7):​c.1203G>T​(p.Arg401Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,229 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: SERPINA7 NM_000354.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.434
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000354.6. 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
	SERPINA7	NM_000354.6	MANE Select	c.1203G>T	p.Arg401Ser	missense	Exon 5 of 5	NP_000345.2	P05543

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA7	ENST00000372563.2	TSL:5 MANE Select	c.1203G>T	p.Arg401Ser	missense	Exon 5 of 5	ENSP00000361644.1	P05543
	SERPINA7	ENST00000327674.8	TSL:1	c.1203G>T	p.Arg401Ser	missense	Exon 4 of 4	ENSP00000329374.4	P05543
	SERPINA7	ENST00000907820.1		c.1233G>T	p.Arg411Ser	missense	Exon 5 of 5	ENSP00000577879.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000109 AC: 2 AN: 182824 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000730

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097229 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 362771

African (AFR) AF: 0.00 AC: 0 AN: 26372

American (AMR) AF: 0.0000568 AC: 2 AN: 35200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19371

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40519

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841241

Other (OTH) AF: 0.00 AC: 0 AN: 46059

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

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	0.30
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.047	T
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.66	T
M_CAP	Pathogenic	0.73	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.43
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.42
Sift	Benign	0.25	T
Sift4G	Benign	0.52	T
Polyphen		0.78	P
Vest4		0.31
MutPred		0.44		Loss of MoRF binding (P = 0.0602)
MVP		0.78
MPC		0.16
ClinPred		0.43	T
GERP RS		-0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.65
gMVP		0.34
Mutation Taster		=70/30	polymorphism

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: rs1197067490; hg19: chrX-105277536;