rs769429068

Variant names:

• chr14-94464807-T-A
• NM_175739.4:c.950A>T

Your query was ambiguous. Multiple possible variants found:

• chr14-94464807-T-A
• chr14-94464807-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_175739.4(SERPINA9):​c.950A>T​(p.Asn317Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,412 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. N317S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SERPINA9 NM_175739.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.78

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA9	NM_175739.4	c.950A>T	p.Asn317Ile	missense_variant	Exon 4 of 5	ENST00000674397.2	NP_783866.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA9	ENST00000674397.2	c.950A>T	p.Asn317Ile	missense_variant	Exon 4 of 5		NM_175739.4	ENSP00000501517.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461412 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727070

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	.;.;.;.;T;.
Eigen	Benign	0.046
Eigen_PC	Benign	-0.019
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.39	T;T;T;T;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.60	D;D;D;D;D;D
MetaSVM	Uncertain	-0.032	T
MutationAssessor	Benign	2.0	.;.;.;.;M;.
PrimateAI	Benign	0.25	T
PROVEAN	Pathogenic	-5.2	D;D;D;D;D;D
REVEL	Uncertain	0.33
Sift	Benign	0.030	D;D;D;D;D;D
Sift4G	Uncertain	0.029	D;D;D;D;D;D
Polyphen		0.80	P;P;.;P;P;P
Vest4		0.43
MutPred		0.61		.;.;.;.;Gain of catalytic residue at L322 (P = 0);.;
MVP		0.89
MPC		0.085
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.52
gMVP		0.19

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: chr14-94931144;