rs2236242

Variant names:

• chr14-94493715-T-A
• rs2236242
• NM_001382267.1:c.905+2658A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382267.1(SERPINA12):​c.905+2658A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,150 control chromosomes in the GnomAD database, including 8,601 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8601 hom., cov: 33)
• Consequence: SERPINA12 NM_001382267.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181
• Publications: 42 publications found

Genes affected

SERPINA12 (HGNC:18359): (serpin family A member 12) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to act upstream of or within negative regulation of gluconeogenesis; positive regulation of signal transduction; and regulation of lipid metabolic process. Predicted to be located in plasma membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SERPINA12 Gene-Disease associations (from GenCC):

• hereditary palmoplantar keratoderma, Gamborg-Nielsen type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA12	NM_001382267.1	c.905+2658A>T		intron_variant	Intron 3 of 4	ENST00000677451.1	NP_001369196.1
SERPINA12	NM_001304461.2	c.905+2658A>T		intron_variant	Intron 3 of 4		NP_001291390.1
SERPINA12	NM_173850.4	c.905+2658A>T		intron_variant	Intron 4 of 5		NP_776249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA12	ENST00000677451.1	c.905+2658A>T		intron_variant	Intron 3 of 4		NM_001382267.1	ENSP00000503935.1
SERPINA12	ENST00000341228.2	c.905+2658A>T		intron_variant	Intron 4 of 5	1		ENSP00000342109.2
SERPINA12	ENST00000556881.5	c.905+2658A>T		intron_variant	Intron 3 of 4	1		ENSP00000451738.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47100 AN: 152032 Hom.: 8597 Cov.: 33

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.326

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.310 AC: 47113 AN: 152150 Hom.: 8601 Cov.: 33 AF XY: 0.311 AC XY: 23162 AN XY: 74374

African (AFR) AF: 0.102 AC: 4258 AN: 41542

American (AMR) AF: 0.397 AC: 6072 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1118 AN: 3472

East Asian (EAS) AF: 0.274 AC: 1418 AN: 5168

South Asian (SAS) AF: 0.335 AC: 1610 AN: 4806

European-Finnish (FIN) AF: 0.437 AC: 4627 AN: 10580

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26949 AN: 67976

Other (OTH) AF: 0.321 AC: 679 AN: 2114

Alfa AF: 0.350 Hom.: 1345

Bravo AF: 0.296

Asia WGS AF: 0.305 AC: 1061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.63
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs2236242; hg19: chr14-94960052;