rs747412188

Variant names:

• chr14-94443166-A-G
• rs747412188
• NM_001080451.2:c.977T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080451.2(SERPINA11):​c.977T>C​(p.Ile326Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SERPINA11 NM_001080451.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.86
• Publications: 0 publications found

Genes affected

SERPINA11 (HGNC:19193): (serpin family A member 11) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SERPINA11 Gene-Disease associations (from GenCC):

• hydrops fetalis

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ENSG00000256357 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4055044).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080451.2. 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
	SERPINA11	NM_001080451.2	MANE Select	c.977T>C	p.Ile326Thr	missense	Exon 4 of 5	NP_001073920.1	Q86U17
	SERPINA11	NM_001429948.1		c.365T>C	p.Ile122Thr	missense	Exon 4 of 5	NP_001416877.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA11	ENST00000334708.4	TSL:1 MANE Select	c.977T>C	p.Ile326Thr	missense	Exon 4 of 5	ENSP00000335024.3	Q86U17
	SERPINA11	ENST00000850861.1		c.986T>C	p.Ile329Thr	missense	Exon 4 of 5	ENSP00000520948.1	A0ABJ7H2Z4
	SERPINA11	ENST00000905969.1		c.977T>C	p.Ile326Thr	missense	Exon 4 of 5	ENSP00000576028.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461682 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727140

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

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

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: 0.00000270 AC: 3 AN: 1111828

Other (OTH) AF: 0.0000331 AC: 2 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

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	0.17
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.076
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.68	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.9
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.42
Sift	Benign	0.29	T
Sift4G	Benign	0.13	T
Polyphen		0.87	P
Vest4		0.27
MutPred		0.78		Loss of stability (P = 0.0113)
MVP		0.55
MPC		0.15
ClinPred		0.77	D
GERP RS		4.7
Varity_R		0.26
gMVP		0.46
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: rs747412188; hg19: chr14-94909503;