rs17090921

Variant names:

• chr14-94467358-G-A
• rs17090921
• NM_175739.4:c.653C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-94467358-G-A
• chr14-94467358-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175739.4(SERPINA9):​c.653C>T​(p.Pro218Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,610,776 control chromosomes in the GnomAD database, including 78,596 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (6444 hom., cov: 33)
  • Exomes 𝑓: 0.31 (72152 hom.)
• Consequence: SERPINA9 NM_175739.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.581
• Publications: 25 publications found

Genes affected

SERPINA9 (HGNC:15995): (serpin family A member 9) Enables serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in cytoplasm and membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00118348).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175739.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA9	NM_175739.4	MANE Select	c.653C>T	p.Pro218Leu	missense	Exon 3 of 5	NP_783866.3
	SERPINA9	NM_001284275.2		c.413C>T	p.Pro138Leu	missense	Exon 3 of 5	NP_001271204.2
	SERPINA9	NM_001042518.2		c.353C>T	p.Pro118Leu	missense	Exon 4 of 6	NP_001035983.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA9	ENST00000674397.2	MANE Select	c.653C>T	p.Pro218Leu	missense	Exon 3 of 5	ENSP00000501517.1
	SERPINA9	ENST00000337425.10	TSL:1	c.707C>T	p.Pro236Leu	missense	Exon 3 of 5	ENSP00000337133.5
	SERPINA9	ENST00000448305.6	TSL:1	c.413C>T	p.Pro138Leu	missense	Exon 3 of 5	ENSP00000414092.2

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42785 AN: 152048 Hom.: 6440 Cov.: 33

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.296

GnomAD2 exomes AF: 0.319 AC: 79139 AN: 248242 AF XY: 0.320

Gnomad AFR exome AF: 0.163

Gnomad AMR exome AF: 0.357

Gnomad ASJ exome AF: 0.301

Gnomad EAS exome AF: 0.440

Gnomad FIN exome AF: 0.319

Gnomad NFE exome AF: 0.301

Gnomad OTH exome AF: 0.316

GnomAD4 exome AF: 0.312 AC: 455417 AN: 1458610 Hom.: 72152 Cov.: 35 AF XY: 0.314 AC XY: 227356 AN XY: 724890

African (AFR) AF: 0.163 AC: 5447 AN: 33408

American (AMR) AF: 0.362 AC: 16174 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 8009 AN: 26110

East Asian (EAS) AF: 0.452 AC: 17885 AN: 39608

South Asian (SAS) AF: 0.352 AC: 30310 AN: 86082

European-Finnish (FIN) AF: 0.323 AC: 17224 AN: 53346

Middle Eastern (MID) AF: 0.232 AC: 1334 AN: 5758

European-Non Finnish (NFE) AF: 0.307 AC: 340110 AN: 1109472

Other (OTH) AF: 0.314 AC: 18924 AN: 60208

GnomAD4 genome AF: 0.281 AC: 42817 AN: 152166 Hom.: 6444 Cov.: 33 AF XY: 0.285 AC XY: 21230 AN XY: 74378

African (AFR) AF: 0.174 AC: 7222 AN: 41530

American (AMR) AF: 0.359 AC: 5490 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1036 AN: 3470

East Asian (EAS) AF: 0.433 AC: 2233 AN: 5154

South Asian (SAS) AF: 0.371 AC: 1791 AN: 4826

European-Finnish (FIN) AF: 0.339 AC: 3598 AN: 10598

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20438 AN: 67990

Other (OTH) AF: 0.303 AC: 639 AN: 2108

Alfa AF: 0.296 Hom.: 22130

Bravo AF: 0.275

TwinsUK AF: 0.307 AC: 1140

ALSPAC AF: 0.319 AC: 1230

ESP6500AA AF: 0.162 AC: 622

ESP6500EA AF: 0.301 AC: 2486

ExAC AF: 0.314 AC: 37964

Asia WGS AF: 0.414 AC: 1440 AN: 3478

EpiCase AF: 0.301

EpiControl AF: 0.299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	11
DANN	Benign	0.93
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.58
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Benign	0.25
Sift	Uncertain	0.011	D
Sift4G	Benign	0.17	T
Polyphen		0.39	B
Vest4		0.18
MPC		0.019
ClinPred		0.034	T
GERP RS		1.9
Varity_R		0.19
gMVP		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17090921; hg19: chr14-94933695; COSMIC: COSV54073248; COSMIC: COSV54073248;