NM_001085.5:c.36C>T

Variant names:

• chr14-94614477-C-T
• rs79181968
• NM_001085.5:c.36C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001085.5(SERPINA3):​c.36C>T​(p.Leu12Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00603 in 1,614,102 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0062 (31 hom.)
• Consequence: SERPINA3 NM_001085.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.682
• Publications: 1 publications found

Genes affected

SERPINA3 (HGNC:16): (serpin family A member 3) The protein encoded by this gene is a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. This gene is one in a cluster of serpin genes located on the q arm of chromosome 14. Polymorphisms in this protein appear to be tissue specific and influence protease targeting. Variations in this protein's sequence have been implicated in Alzheimer's disease, and deficiency of this protein has been associated with liver disease. Mutations have been identified in patients with Parkinson disease and chronic obstructive pulmonary disease. [provided by RefSeq, Jun 2020]

ENSG00000273259 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 14-94614477-C-T is Benign according to our data. Variant chr14-94614477-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 789642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.682 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 31 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085.5. 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
	SERPINA3	NM_001085.5	MANE Select	c.36C>T	p.Leu12Leu	synonymous	Exon 2 of 5	NP_001076.2	P01011-1
	SERPINA3	NM_001384672.1		c.36C>T	p.Leu12Leu	synonymous	Exon 2 of 5	NP_001371601.1	P01011-1
	SERPINA3	NM_001384673.1		c.36C>T	p.Leu12Leu	synonymous	Exon 3 of 6	NP_001371602.1	P01011-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA3	ENST00000393078.5	TSL:1 MANE Select	c.36C>T	p.Leu12Leu	synonymous	Exon 2 of 5	ENSP00000376793.3	P01011-1
	SERPINA3	ENST00000393080.8	TSL:1	c.36C>T	p.Leu12Leu	synonymous	Exon 2 of 5	ENSP00000376795.4	P01011-1
	ENSG00000273259	ENST00000553947.1	TSL:2	n.*862C>T		non_coding_transcript_exon	Exon 5 of 8	ENSP00000452367.2	G3V5I3

Frequencies

GnomAD3 genomes AF: 0.00443 AC: 674 AN: 152134 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00808

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00753

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00657

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00502 AC: 1262 AN: 251270 AF XY: 0.00517

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.00863

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00763

Gnomad NFE exome AF: 0.00677

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00620 AC: 9067 AN: 1461850 Hom.: 31 Cov.: 35 AF XY: 0.00612 AC XY: 4453 AN XY: 727220

African (AFR) AF: 0.00122 AC: 41 AN: 33480

American (AMR) AF: 0.00206 AC: 92 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00995 AC: 260 AN: 26136

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

South Asian (SAS) AF: 0.00464 AC: 400 AN: 86256

European-Finnish (FIN) AF: 0.00813 AC: 434 AN: 53404

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.00672 AC: 7475 AN: 1111988

Other (OTH) AF: 0.00596 AC: 360 AN: 60394

GnomAD4 genome AF: 0.00443 AC: 674 AN: 152252 Hom.: 0 Cov.: 32 AF XY: 0.00438 AC XY: 326 AN XY: 74444

African (AFR) AF: 0.00116 AC: 48 AN: 41556

American (AMR) AF: 0.00314 AC: 48 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00808 AC: 28 AN: 3466

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5154

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4824

European-Finnish (FIN) AF: 0.00753 AC: 80 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00657 AC: 447 AN: 68010

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00692 Hom.: 1

Bravo AF: 0.00438

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00551

EpiControl AF: 0.00486

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.75
DANN	Benign	0.66
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs79181968; hg19: chr14-95080814;