rs61754490
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_000354.6(SERPINA7):c.986A>T(p.Tyr329Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0019 in 1,206,818 control chromosomes in the GnomAD database, including 7 homozygotes. There are 709 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.0014 ( 0 hom., 44 hem., cov: 23)
Exomes 𝑓: 0.0019 ( 7 hom. 665 hem. )
Consequence
SERPINA7
NM_000354.6 missense
NM_000354.6 missense
Scores
1
15
Clinical Significance
Conservation
PhyloP100: 5.51
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.08913022).
BS2
?
High Hemizygotes in GnomAd at 44 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINA7 | NM_000354.6 | c.986A>T | p.Tyr329Phe | missense_variant | 4/5 | ENST00000372563.2 | |
SERPINA7 | XM_006724683.3 | c.986A>T | p.Tyr329Phe | missense_variant | 4/5 | ||
SERPINA7 | XM_005262180.5 | c.986A>T | p.Tyr329Phe | missense_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINA7 | ENST00000372563.2 | c.986A>T | p.Tyr329Phe | missense_variant | 4/5 | 5 | NM_000354.6 | P1 | |
SERPINA7 | ENST00000327674.8 | c.986A>T | p.Tyr329Phe | missense_variant | 3/4 | 1 | P1 | ||
SERPINA7 | ENST00000487487.1 | n.259A>T | non_coding_transcript_exon_variant | 2/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00141 AC: 158AN: 112087Hom.: 0 Cov.: 23 AF XY: 0.00128 AC XY: 44AN XY: 34279
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?
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GnomAD3 exomes AF: 0.00101 AC: 185AN: 182839Hom.: 0 AF XY: 0.00107 AC XY: 72AN XY: 67523
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GnomAD4 exome AF: 0.00195 AC: 2130AN: 1094680Hom.: 7 Cov.: 30 AF XY: 0.00185 AC XY: 665AN XY: 360250
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GnomAD4 genome ? AF: 0.00141 AC: 158AN: 112138Hom.: 0 Cov.: 23 AF XY: 0.00128 AC XY: 44AN XY: 34340
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ESP6500AA
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Thyroxine-binding globulin, Chicago Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 24, 1995 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T
FATHMM_MKL
Benign
N
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
A;A
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at