14-94464768-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_175739.4(SERPINA9):​c.989T>A​(p.Val330Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>A	p.Val330Asp	missense	Exon 4 of 5	NP_783866.3
	SERPINA9	NM_001284275.2		c.749T>A	p.Val250Asp	missense	Exon 4 of 5	NP_001271204.2
	SERPINA9	NM_001042518.2		c.689T>A	p.Val230Asp	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>A	p.Val330Asp	missense	Exon 4 of 5	ENSP00000501517.1
	SERPINA9	ENST00000337425.10	TSL:1	c.1043T>A	p.Val348Asp	missense	Exon 4 of 5	ENSP00000337133.5
	SERPINA9	ENST00000448305.6	TSL:1	c.749T>A	p.Val250Asp	missense	Exon 4 of 5	ENSP00000414092.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461328 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 727002

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111534

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 162795

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	20
DANN	Benign	0.70
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Uncertain	0.29	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		0.90
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.017	D
Polyphen		0.042	B
Vest4		0.40
MutPred		0.81		Gain of disorder (P = 0.0078)
MVP		0.26
MPC		0.019
ClinPred		0.73	D
GERP RS		2.1
Varity_R		0.61
gMVP		0.62
Mutation Taster		=94/6	polymorphism

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;