rs11627075

Variant names:

• chr14-94505905-C-A
• rs11627075
• NM_001382267.1:c.-34+3437G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-94505905-C-A
• chr14-94505905-C-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.-34+3437G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0843 in 152,256 control chromosomes in the GnomAD database, including 609 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 0.084 (609 hom., cov: 33)
• Consequence: SERPINA12 NM_001382267.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA12	NM_001382267.1	c.-34+3437G>T		intron_variant	Intron 1 of 4	ENST00000677451.1	NP_001369196.1
SERPINA12	NM_173850.4	c.-17-7491G>T		intron_variant	Intron 2 of 5		NP_776249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA12	ENST00000677451.1	c.-34+3437G>T		intron_variant	Intron 1 of 4		NM_001382267.1	ENSP00000503935.1
SERPINA12	ENST00000341228.2	c.-17-7491G>T		intron_variant	Intron 2 of 5	1		ENSP00000342109.2

Frequencies

GnomAD3 genomes AF: 0.0843 AC: 12824 AN: 152138 Hom.: 610 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0626

Gnomad ASJ AF: 0.0919

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.0658

Gnomad FIN AF: 0.0792

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.0799

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

GnomAD4 genome AF: 0.0843 AC: 12835 AN: 152256 Hom.: 609 Cov.: 33 AF XY: 0.0838 AC XY: 6240 AN XY: 74444

African (AFR) AF: 0.110 AC: 4573 AN: 41546

American (AMR) AF: 0.0625 AC: 957 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0919 AC: 319 AN: 3472

East Asian (EAS) AF: 0.0209 AC: 108 AN: 5178

South Asian (SAS) AF: 0.0659 AC: 318 AN: 4826

European-Finnish (FIN) AF: 0.0792 AC: 840 AN: 10608

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0811 AC: 5519 AN: 68010

Other (OTH) AF: 0.0791 AC: 167 AN: 2112

Alfa AF: 0.0788 Hom.: 1360

Bravo AF: 0.0829

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.048
DANN	Benign	0.58
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11627075; hg19: chr14-94972242;