14-94446536-T-A

Variant names:

• chr14-94446536-T-A
• NM_001080451.2:c.712A>T

Variant summary

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

The NM_001080451.2(SERPINA11):​c.712A>T​(p.Thr238Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SERPINA11 NM_001080451.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.69

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]

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
SERPINA11	NM_001080451.2	c.712A>T	p.Thr238Ser	missense_variant	Exon 3 of 5	ENST00000334708.4	NP_001073920.1
SERPINA11	NM_001429948.1	c.100A>T	p.Thr34Ser	missense_variant	Exon 3 of 5		NP_001416877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA11	ENST00000334708.4	c.712A>T	p.Thr238Ser	missense_variant	Exon 3 of 5	1	NM_001080451.2	ENSP00000335024.3
ENSG00000256357	ENST00000536735.1	n.171+14795T>A		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.712A>T (p.T238S) alteration is located in exon 3 (coding exon 2) of the SERPINA11 gene. This alteration results from a A to T substitution at nucleotide position 712, causing the threonine (T) at amino acid position 238 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.046
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	0.23	D
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.018	D
Sift4G	Benign	0.19	T
Polyphen		0.76	P
Vest4		0.10
MutPred		0.49		Gain of disorder (P = 0.0252);
MVP		0.71
MPC		0.052
ClinPred		0.68	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.38		Position offset: -12

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: chr14-94912873;