Genetic Variant SERPINA6:p.Pro268Pro (chr14-94309816-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001756.4(SERPINA6):c.804G>A(p.Pro268Pro) 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 (no stars).

Frequency

Genomes: 𝑓 0.0077 ( 18 hom., cov: 32)

Exomes 𝑓: 0.00096 ( 17 hom. )

Consequence

SERPINA6
NM_001756.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided 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]

SERPINA6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

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 no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-7.23 with no splicing effect.

BS1

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

High Homozygotes in GnomAd4 at 18 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA6	NM_001756.4 link	c.804G>A	p.Pro268Pro	synonymous_variant	Exon 3 of 5	ENST00000341584.4	NP_001747.3	P08185A0A2Z4LCH4
SERPINA6	XM_047431827.1 link	c.975G>A	p.Pro325Pro	synonymous_variant	Exon 3 of 5		XP_047287783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SERPINA6	ENST00000341584.4 link	c.804G>A	p.Pro268Pro	synonymous_variant	Exon 3 of 5	1	NM_001756.4	ENSP00000342850.3	P08185
SERPINA6	ENST00000555056.1 link	n.*116G>A		non_coding_transcript_exon_variant	Exon 3 of 5	2		ENSP00000451045.1	G3V350
SERPINA6	ENST00000555056.1 link	n.*116G>A		3_prime_UTR_variant	Exon 3 of 5	2		ENSP00000451045.1	G3V350

Frequencies

GnomAD3 genomes

AF:

0.00766

AC:

1166

AN:

152144

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00768

AC:

1169

AN:

152262

Hom.:

Cov.:

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.:

Bravo

AF:

0.00875

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SERPINA6-related disorder

Benign:1

Sep 30, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over