14-94614699-C-T

Variant names:

• chr14-94614699-C-T
• rs61737405
• NM_001085.5:c.258C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001085.5(SERPINA3):​c.258C>T​(p.Phe86Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000957 in 1,614,180 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00058 (7 hom.)
• Consequence: SERPINA3 NM_001085.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.34
• Publications: 2 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 14-94614699-C-T is Benign according to our data. Variant chr14-94614699-C-T is described in ClinVar as Benign. ClinVar VariationId is 789820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.34 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 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.258C>T	p.Phe86Phe	synonymous	Exon 2 of 5	NP_001076.2	P01011-1
	SERPINA3	NM_001384672.1		c.258C>T	p.Phe86Phe	synonymous	Exon 2 of 5	NP_001371601.1	P01011-1
	SERPINA3	NM_001384673.1		c.258C>T	p.Phe86Phe	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.258C>T	p.Phe86Phe	synonymous	Exon 2 of 5	ENSP00000376793.3	P01011-1
	SERPINA3	ENST00000393080.8	TSL:1	c.258C>T	p.Phe86Phe	synonymous	Exon 2 of 5	ENSP00000376795.4	P01011-1
	ENSG00000273259	ENST00000553947.1	TSL:2	n.*1084C>T		non_coding_transcript_exon	Exon 5 of 8	ENSP00000452367.2	G3V5I3

Frequencies

GnomAD3 genomes AF: 0.00453 AC: 690 AN: 152168 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00130 AC: 328 AN: 251352 AF XY: 0.000972

Gnomad AFR exome AF: 0.0150

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.00278

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000583 AC: 853 AN: 1461894 Hom.: 7 Cov.: 35 AF XY: 0.000550 AC XY: 400 AN XY: 727248

African (AFR) AF: 0.0153 AC: 513 AN: 33480

American (AMR) AF: 0.00101 AC: 45 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00287 AC: 75 AN: 26136

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

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.000119 AC: 132 AN: 1112012

Other (OTH) AF: 0.00119 AC: 72 AN: 60396

GnomAD4 genome AF: 0.00454 AC: 692 AN: 152286 Hom.: 5 Cov.: 32 AF XY: 0.00420 AC XY: 313 AN XY: 74480

African (AFR) AF: 0.0153 AC: 635 AN: 41564

American (AMR) AF: 0.00189 AC: 29 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68022

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00217 Hom.: 0

Bravo AF: 0.00476

EpiCase AF: 0.000273

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	5.6
DANN	Benign	0.69
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs61737405; hg19: chr14-95081036;