rs11628722

Variant names:

• chr14-94464768-A-G
• rs11628722
• NM_175739.4:c.989T>C

Your query was ambiguous. Multiple possible variants found:

• chr14-94464768-A-G
• chr14-94464768-A-T

Variant summary

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

The NM_175739.4(SERPINA9):​c.989T>C​(p.Val330Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,612,534 control chromosomes in the GnomAD database, including 533,131 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.71 (40562 hom., cov: 32)
  • Exomes 𝑓: 0.82 (492569 hom.)
• Consequence: SERPINA9 NM_175739.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.900
• Publications: 33 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]

ENSG00000256357 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.8559922E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.835 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA9	NM_175739.4	MANE Select	c.989T>C	p.Val330Ala	missense	Exon 4 of 5	NP_783866.3
	SERPINA9	NM_001284275.2		c.749T>C	p.Val250Ala	missense	Exon 4 of 5	NP_001271204.2
	SERPINA9	NM_001042518.2		c.689T>C	p.Val230Ala	missense	Exon 5 of 6	NP_001035983.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA9	ENST00000674397.2	MANE Select	c.989T>C	p.Val330Ala	missense	Exon 4 of 5	ENSP00000501517.1
	SERPINA9	ENST00000337425.10	TSL:1	c.1043T>C	p.Val348Ala	missense	Exon 4 of 5	ENSP00000337133.5
	SERPINA9	ENST00000448305.6	TSL:1	c.749T>C	p.Val250Ala	missense	Exon 4 of 5	ENSP00000414092.2

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107912 AN: 151966 Hom.: 40552 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.936

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.855

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.742

GnomAD2 exomes AF: 0.776 AC: 193539 AN: 249310 AF XY: 0.790

Gnomad AFR exome AF: 0.433

Gnomad AMR exome AF: 0.693

Gnomad ASJ exome AF: 0.758

Gnomad EAS exome AF: 0.625

Gnomad FIN exome AF: 0.852

Gnomad NFE exome AF: 0.836

Gnomad OTH exome AF: 0.795

GnomAD4 exome AF: 0.818 AC: 1194100 AN: 1460450 Hom.: 492569 Cov.: 37 AF XY: 0.820 AC XY: 596127 AN XY: 726634

African (AFR) AF: 0.428 AC: 14325 AN: 33452

American (AMR) AF: 0.702 AC: 31352 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 19869 AN: 26124

East Asian (EAS) AF: 0.619 AC: 24548 AN: 39670

South Asian (SAS) AF: 0.859 AC: 74011 AN: 86200

European-Finnish (FIN) AF: 0.855 AC: 45659 AN: 53416

Middle Eastern (MID) AF: 0.779 AC: 4493 AN: 5764

European-Non Finnish (NFE) AF: 0.839 AC: 932056 AN: 1110820

Other (OTH) AF: 0.792 AC: 47787 AN: 60344

GnomAD4 genome AF: 0.710 AC: 107967 AN: 152084 Hom.: 40562 Cov.: 32 AF XY: 0.712 AC XY: 52904 AN XY: 74354

African (AFR) AF: 0.446 AC: 18474 AN: 41440

American (AMR) AF: 0.744 AC: 11367 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.757 AC: 2626 AN: 3470

East Asian (EAS) AF: 0.614 AC: 3173 AN: 5166

South Asian (SAS) AF: 0.857 AC: 4130 AN: 4820

European-Finnish (FIN) AF: 0.855 AC: 9058 AN: 10590

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56485 AN: 68000

Other (OTH) AF: 0.746 AC: 1576 AN: 2114

Alfa AF: 0.784 Hom.: 162795

Bravo AF: 0.687

ESP6500AA AF: 0.464 AC: 1705

ESP6500EA AF: 0.834 AC: 6820

ExAC AF: 0.777 AC: 93866

Asia WGS AF: 0.737 AC: 2563 AN: 3478

EpiCase AF: 0.824

EpiControl AF: 0.825

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.0
DANN	Benign	0.48
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0052	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0000019	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.73	N
PhyloP100		0.90
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.27
Sift	Benign	1.0	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.025
MPC		0.016
ClinPred		0.00075	T
GERP RS		2.1
Varity_R		0.027
gMVP		0.18
Mutation Taster		=100/0	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: rs11628722; hg19: chr14-94931105; COSMIC: COSV100097934; COSMIC: COSV100097934;