rs199738408

Variant names:

• chr14-94463217-C-A
• NM_175739.4:c.1130G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-94463217-C-A
• chr14-94463217-C-G
• chr14-94463217-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_175739.4(SERPINA9):​c.1130G>T​(p.Arg377Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R377Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SERPINA9 NM_175739.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26866072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA9	NM_175739.4	c.1130G>T	p.Arg377Leu	missense_variant	Exon 5 of 5	ENST00000674397.2	NP_783866.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA9	ENST00000674397.2	c.1130G>T	p.Arg377Leu	missense_variant	Exon 5 of 5		NM_175739.4	ENSP00000501517.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.0052	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	14
DANN	Benign	0.85
DEOGEN2	Benign	0.055	.;.;.;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.79	T;T;T;T;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.27	T;T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.5	.;.;.;.;L
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.0	N;N;D;N;N
REVEL	Benign	0.20
Sift	Benign	0.38	T;T;T;T;T
Sift4G	Benign	0.73	T;T;T;T;T
Polyphen		0.065	B;B;.;B;.
Vest4		0.43
MutPred		0.73		.;.;.;Gain of ubiquitination at K397 (P = 0.0472);.;
MVP		0.36
MPC		0.10
ClinPred		0.33	T
GERP RS		2.2
Varity_R		0.21
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-94929554;