14-94463179-T-C

Variant names:

• chr14-94463179-T-C
• rs200415975
• NM_175739.4:c.1168A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_175739.4(SERPINA9):​c.1168A>G​(p.Asn390Asp) 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. 16/22 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. N390Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SERPINA9 NM_175739.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13525239).

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.1168A>G	p.Asn390Asp	missense	Exon 5 of 5	NP_783866.3	Q86WD7-1
	SERPINA9	NM_001284275.2		c.928A>G	p.Asn310Asp	missense	Exon 5 of 5	NP_001271204.2	Q86WD7-6
	SERPINA9	NM_001042518.2		c.868A>G	p.Asn290Asp	missense	Exon 6 of 6	NP_001035983.2	A0A6Q8JH89

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA9	ENST00000674397.2	MANE Select	c.1168A>G	p.Asn390Asp	missense	Exon 5 of 5	ENSP00000501517.1	Q86WD7-1
	SERPINA9	ENST00000337425.10	TSL:1	c.1222A>G	p.Asn408Asp	missense	Exon 5 of 5	ENSP00000337133.5	Q86WD7-7
	SERPINA9	ENST00000448305.6	TSL:1	c.928A>G	p.Asn310Asp	missense	Exon 5 of 5	ENSP00000414092.2	Q86WD7-6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461814 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727216

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111936

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.49
DANN	Benign	0.91
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	-0.020	N
PhyloP100		0.043
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.18
Sift	Benign	0.44	T
Sift4G	Benign	0.30	T
Polyphen		0.14	B
Vest4		0.11
MutPred		0.65		Gain of sheet (P = 0.0827)
MVP		0.41
MPC		0.016
ClinPred		0.16	T
GERP RS		-1.1
Varity_R		0.099
gMVP		0.14
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: rs200415975; hg19: chr14-94929516;