rs752814721

Variant names:

• chr14-94467127-C-G
• rs752814721
• NM_175739.4:c.884G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-94467127-C-G
• chr14-94467127-C-T

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.884G>C​(p.Ser295Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,848 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S295N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: SERPINA9 NM_175739.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.705
• 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]

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=0.1214416).

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.884G>C	p.Ser295Thr	missense	Exon 3 of 5	NP_783866.3	Q86WD7-1
	SERPINA9	NM_001284275.2		c.644G>C	p.Ser215Thr	missense	Exon 3 of 5	NP_001271204.2	Q86WD7-6
	SERPINA9	NM_001042518.2		c.584G>C	p.Ser195Thr	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.884G>C	p.Ser295Thr	missense	Exon 3 of 5	ENSP00000501517.1	Q86WD7-1
	SERPINA9	ENST00000337425.10	TSL:1	c.938G>C	p.Ser313Thr	missense	Exon 3 of 5	ENSP00000337133.5	Q86WD7-7
	SERPINA9	ENST00000448305.6	TSL:1	c.644G>C	p.Ser215Thr	missense	Exon 3 of 5	ENSP00000414092.2	Q86WD7-6

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 249238 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461612 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727090

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000719 AC: 8 AN: 1111886

Other (OTH) AF: 0.0000166 AC: 1 AN: 60378

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152236 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74378

African (AFR) AF: 0.00 AC: 0 AN: 41462

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

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: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	10
DANN	Benign	0.92
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.095	N
PhyloP100		-0.70
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.20
Sift	Benign	0.15	T
Sift4G	Benign	0.45	T
Polyphen		0.70	P
Vest4		0.16
MutPred		0.42		Gain of catalytic residue at L298 (P = 0.0431)
MVP		0.84
MPC		0.029
ClinPred		0.22	T
GERP RS		2.0
Varity_R		0.083
gMVP		0.094
Mutation Taster		=99/1	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: rs752814721; hg19: chr14-94933464;