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GeneBe

14-94309816-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001756.4(SERPINA6):c.804G>A(p.Pro268=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,614,144 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 18 hom., cov: 32)
Exomes 𝑓: 0.00096 ( 17 hom. )

Consequence

SERPINA6
NM_001756.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -7.23
Variant links:
Genes affected
SERPINA6 (HGNC:1540): (serpin family A member 6) This gene encodes an alpha-globulin protein with corticosteroid-binding properties. This is the major transport protein for glucorticoids and progestins in the blood of most vertebrates. The gene localizes to a chromosomal region containing several closely related serine protease inhibitors which may have evolved by duplication events. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 14-94309816-C-T is Benign according to our data. Variant chr14-94309816-C-T is described in ClinVar as [Benign]. Clinvar id is 3042040.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-7.23 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00768 (1169/152262) while in subpopulation AFR AF= 0.0268 (1112/41546). AF 95% confidence interval is 0.0255. There are 18 homozygotes in gnomad4. There are 555 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 18 SD gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SERPINA6NM_001756.4 linkuse as main transcriptc.804G>A p.Pro268= synonymous_variant 3/5 ENST00000341584.4
SERPINA6XM_047431827.1 linkuse as main transcriptc.975G>A p.Pro325= synonymous_variant 3/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SERPINA6ENST00000341584.4 linkuse as main transcriptc.804G>A p.Pro268= synonymous_variant 3/51 NM_001756.4 P1
SERPINA6ENST00000555056.1 linkuse as main transcriptc.*116G>A 3_prime_UTR_variant, NMD_transcript_variant 3/52

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00766
AC:
1166
AN:
152144
Hom.:
18
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0267
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00183
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00478
GnomAD3 exomes
AF:
0.00226
AC:
567
AN:
251304
Hom.:
5
AF XY:
0.00166
AC XY:
226
AN XY:
135814
show subpopulations
Gnomad AFR exome
AF:
0.0276
Gnomad AMR exome
AF:
0.00176
Gnomad ASJ exome
AF:
0.00179
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000523
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000150
Gnomad OTH exome
AF:
0.00114
GnomAD4 exome
AF:
0.000964
AC:
1409
AN:
1461882
Hom.:
17
Cov.:
33
AF XY:
0.000880
AC XY:
640
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0306
Gnomad4 AMR exome
AF:
0.00188
Gnomad4 ASJ exome
AF:
0.00207
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000649
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000549
Gnomad4 OTH exome
AF:
0.00192
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00768
AC:
1169
AN:
152262
Hom.:
18
Cov.:
32
AF XY:
0.00746
AC XY:
555
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.0268
Gnomad4 AMR
AF:
0.00177
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.00409
Hom.:
2
Bravo
AF:
0.00875
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

SERPINA6-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesSep 30, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
Cadd
Benign
0.52
Dann
Benign
0.70
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61754488; hg19: chr14-94776153; API