rs17826465

Variant names:

• chr14-94614744-A-G
• rs17826465
• NM_001085.5:c.303A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001085.5(SERPINA3):​c.303A>G​(p.Lys101Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 1,614,086 control chromosomes in the GnomAD database, including 8,645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.073 (536 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8109 hom.)
• Consequence: SERPINA3 NM_001085.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.311
• Publications: 11 publications found

Genes affected

SERPINA3 (HGNC:16): (serpin family A member 3) The protein encoded by this gene is a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. This gene is one in a cluster of serpin genes located on the q arm of chromosome 14. Polymorphisms in this protein appear to be tissue specific and influence protease targeting. Variations in this protein's sequence have been implicated in Alzheimer's disease, and deficiency of this protein has been associated with liver disease. Mutations have been identified in patients with Parkinson disease and chronic obstructive pulmonary disease. [provided by RefSeq, Jun 2020]

ENSG00000273259 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 14-94614744-A-G is Benign according to our data. Variant chr14-94614744-A-G is described in ClinVar as Benign. ClinVar VariationId is 403428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.311 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085.5. 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
	SERPINA3	NM_001085.5	MANE Select	c.303A>G	p.Lys101Lys	synonymous	Exon 2 of 5	NP_001076.2	P01011-1
	SERPINA3	NM_001384672.1		c.303A>G	p.Lys101Lys	synonymous	Exon 2 of 5	NP_001371601.1	P01011-1
	SERPINA3	NM_001384673.1		c.303A>G	p.Lys101Lys	synonymous	Exon 3 of 6	NP_001371602.1	P01011-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA3	ENST00000393078.5	TSL:1 MANE Select	c.303A>G	p.Lys101Lys	synonymous	Exon 2 of 5	ENSP00000376793.3	P01011-1
	SERPINA3	ENST00000393080.8	TSL:1	c.303A>G	p.Lys101Lys	synonymous	Exon 2 of 5	ENSP00000376795.4	P01011-1
	ENSG00000273259	ENST00000553947.1	TSL:2	n.*1129A>G		non_coding_transcript_exon	Exon 5 of 8	ENSP00000452367.2	G3V5I3

Frequencies

GnomAD3 genomes AF: 0.0730 AC: 11111 AN: 152102 Hom.: 539 Cov.: 32

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.0751

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.0713

Gnomad FIN AF: 0.0406

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0891

GnomAD2 exomes AF: 0.0809 AC: 20330 AN: 251304 AF XY: 0.0836

Gnomad AFR exome AF: 0.0203

Gnomad AMR exome AF: 0.0592

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.00272

Gnomad FIN exome AF: 0.0439

Gnomad NFE exome AF: 0.114

Gnomad OTH exome AF: 0.0959

GnomAD4 exome AF: 0.101 AC: 147080 AN: 1461866 Hom.: 8109 Cov.: 36 AF XY: 0.100 AC XY: 73043 AN XY: 727230

African (AFR) AF: 0.0185 AC: 618 AN: 33480

American (AMR) AF: 0.0607 AC: 2716 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0993 AC: 2596 AN: 26136

East Asian (EAS) AF: 0.00161 AC: 64 AN: 39700

South Asian (SAS) AF: 0.0780 AC: 6724 AN: 86258

European-Finnish (FIN) AF: 0.0475 AC: 2537 AN: 53414

Middle Eastern (MID) AF: 0.143 AC: 827 AN: 5768

European-Non Finnish (NFE) AF: 0.112 AC: 124927 AN: 1111990

Other (OTH) AF: 0.101 AC: 6071 AN: 60396

GnomAD4 genome AF: 0.0729 AC: 11100 AN: 152220 Hom.: 536 Cov.: 32 AF XY: 0.0698 AC XY: 5195 AN XY: 74450

African (AFR) AF: 0.0212 AC: 879 AN: 41548

American (AMR) AF: 0.0750 AC: 1147 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3472

East Asian (EAS) AF: 0.00425 AC: 22 AN: 5172

South Asian (SAS) AF: 0.0713 AC: 344 AN: 4822

European-Finnish (FIN) AF: 0.0406 AC: 431 AN: 10606

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7509 AN: 67982

Other (OTH) AF: 0.0891 AC: 188 AN: 2110

Alfa AF: 0.103 Hom.: 2034

Bravo AF: 0.0737

Asia WGS AF: 0.0560 AC: 194 AN: 3478

EpiCase AF: 0.121

EpiControl AF: 0.121

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	SERPINA3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.46
PhyloP100		0.31
Mutation Taster		=99/1	polymorphism (auto)

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: rs17826465; hg19: chr14-95081081; COSMIC: COSV67585529; COSMIC: COSV67585529;