NM_175739.4:c.764A>G

Variant names:

• chr14-94467247-T-C
• rs771379037
• NM_175739.4:c.764A>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.764A>G​(p.Asn255Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SERPINA9 NM_175739.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.746
• Publications: 0 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]

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=0.10346708).

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.764A>G	p.Asn255Ser	missense	Exon 3 of 5	NP_783866.3	Q86WD7-1
	SERPINA9	NM_001284275.2		c.524A>G	p.Asn175Ser	missense	Exon 3 of 5	NP_001271204.2	Q86WD7-6
	SERPINA9	NM_001042518.2		c.464A>G	p.Asn155Ser	missense	Exon 4 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.764A>G	p.Asn255Ser	missense	Exon 3 of 5	ENSP00000501517.1	Q86WD7-1
	SERPINA9	ENST00000337425.10	TSL:1	c.818A>G	p.Asn273Ser	missense	Exon 3 of 5	ENSP00000337133.5	Q86WD7-7
	SERPINA9	ENST00000448305.6	TSL:1	c.524A>G	p.Asn175Ser	missense	Exon 3 of 5	ENSP00000414092.2	Q86WD7-6

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0 AN XY: 727246

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: 86256

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: 1112012

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74360

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.69
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	-0.15	N
PhyloP100		0.75
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.23
Sift	Benign	0.60	T
Sift4G	Benign	0.84	T
Polyphen		0.045	B
Vest4		0.036
MutPred		0.45		Gain of catalytic residue at D251 (P = 0)
MVP		0.46
MPC		0.016
ClinPred		0.052	T
GERP RS		1.5
Varity_R		0.037
gMVP		0.028
Mutation Taster		=96/4	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: rs771379037; hg19: chr14-94933584;