14-94491377-G-T

Variant names:

• chr14-94491377-G-T
• rs1998207
• NM_001382267.1:c.906-1610C>A

Variant summary

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

The NM_173850.4(SERPINA12):​c.906-1610C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 151,944 control chromosomes in the GnomAD database, including 9,249 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 0.34 (9249 hom., cov: 32)
• Consequence: SERPINA12 NM_173850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 14 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173850.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA12	NM_001382267.1	MANE Select	c.906-1610C>A		intron	N/A	NP_001369196.1
	SERPINA12	NM_001304461.2		c.906-1610C>A		intron	N/A	NP_001291390.1
	SERPINA12	NM_173850.4		c.906-1610C>A		intron	N/A	NP_776249.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA12	ENST00000677451.1	MANE Select	c.906-1610C>A		intron	N/A	ENSP00000503935.1
	SERPINA12	ENST00000341228.2	TSL:1	c.906-1610C>A		intron	N/A	ENSP00000342109.2
	SERPINA12	ENST00000556881.5	TSL:1	c.906-1610C>A		intron	N/A	ENSP00000451738.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51801 AN: 151826 Hom.: 9224 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.341 AC: 51866 AN: 151944 Hom.: 9249 Cov.: 32 AF XY: 0.343 AC XY: 25486 AN XY: 74260

African (AFR) AF: 0.438 AC: 18147 AN: 41424

American (AMR) AF: 0.280 AC: 4274 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3470

East Asian (EAS) AF: 0.443 AC: 2287 AN: 5158

South Asian (SAS) AF: 0.433 AC: 2077 AN: 4792

European-Finnish (FIN) AF: 0.234 AC: 2465 AN: 10554

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19998 AN: 67970

Other (OTH) AF: 0.358 AC: 755 AN: 2106

Alfa AF: 0.313 Hom.: 14159

Bravo AF: 0.347

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.078
DANN	Benign	0.16
PhyloP100		-2.1
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: rs1998207; hg19: chr14-94957714;