chr14-94464768-A-G

Position:

• chr14-94464768-A-G

Variant summary

Our verdict is Benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINA9	NM_175739.4	c.989T>C	p.Val330Ala	missense_variant	4/5	ENST00000674397.2	NP_783866.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINA9	ENST00000674397.2	c.989T>C	p.Val330Ala	missense_variant	4/5		NM_175739.4	ENSP00000501517.1

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

GnomAD3 exomes AF: 0.776 AC: 193539 AN: 249310 Hom.: 76851 AF XY: 0.790 AC XY: 106873 AN XY: 135274

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 SAS exome AF: 0.859

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

Gnomad4 AFR exome AF: 0.428

Gnomad4 AMR exome AF: 0.702

Gnomad4 ASJ exome AF: 0.761

Gnomad4 EAS exome AF: 0.619

Gnomad4 SAS exome AF: 0.859

Gnomad4 FIN exome AF: 0.855

Gnomad4 NFE exome AF: 0.839

Gnomad4 OTH exome AF: 0.792

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

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.757

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.857

Gnomad4 FIN AF: 0.855

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.746

Alfa AF: 0.801 Hom.: 120567

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 v4.3

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;T;T;T;T;T
MetaRNN	Benign	0.0000019	T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.73	.;.;.;.;N;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.29	N;N;N;N;N;N
REVEL	Benign	0.27
Sift	Benign	1.0	T;T;T;T;T;T
Sift4G	Benign	0.42	T;T;T;T;T;T
Polyphen		0.0	B;B;.;B;B;B
Vest4		0.025
MPC		0.016
ClinPred		0.00075	T
GERP RS		2.1
Varity_R		0.027
gMVP		0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs11628722; hg19: chr14-94931105; COSMIC: COSV100097934; COSMIC: COSV100097934;