rs138313759

Variant names:

• chr8-67434104-T-C
• rs138313759
• NM_020361.5:c.975A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-67434104-T-C
• chr8-67434104-T-A

Variant summary

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

The NM_020361.5(CPA6):​c.975A>G​(p.Ala325Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00456 in 1,613,888 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (28 hom.)
• Consequence: CPA6 NM_020361.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.22
• Publications: 2 publications found

Genes affected

CPA6 (HGNC:17245): (carboxypeptidase A6) The gene encodes a member of the peptidase M14 family of metallocarboxypeptidases. The encoded preproprotein is proteolytically processed to generate the mature enzyme, which catalyzes the release of large hydrophobic C-terminal amino acids. This enzyme has functions ranging from digestion of food to selective biosynthesis of neuroendocrine peptides. Mutations in this gene may be linked to epilepsy and febrile seizures, and a translocation t(6;8)(q26;q13) involving this gene has been associated with Duane retraction syndrome. [provided by RefSeq, May 2016]

ARFGEF1-DT (HGNC:55237): (ARFGEF1 divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 8-67434104-T-C is Benign according to our data. Variant chr8-67434104-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 284180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.22 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 28 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020361.5. 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
	CPA6	NM_020361.5	MANE Select	c.975A>G	p.Ala325Ala	synonymous	Exon 9 of 11	NP_065094.3
	ARFGEF1-DT	NR_136224.1		n.470-8106T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA6	ENST00000297770.10	TSL:1 MANE Select	c.975A>G	p.Ala325Ala	synonymous	Exon 9 of 11	ENSP00000297770.4	Q8N4T0-1
	CPA6	ENST00000479862.6	TSL:1	n.*435-11413A>G		intron	N/A	ENSP00000419016.2	Q8N4T0-3
	CPA6	ENST00000956854.1		c.1068A>G	p.Ala356Ala	synonymous	Exon 10 of 12	ENSP00000626913.1

Frequencies

GnomAD3 genomes AF: 0.00289 AC: 440 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00492

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00301 AC: 756 AN: 251478 AF XY: 0.00307

Gnomad AFR exome AF: 0.000984

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00228

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00305

Gnomad NFE exome AF: 0.00491

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00473 AC: 6916 AN: 1461542 Hom.: 28 Cov.: 31 AF XY: 0.00465 AC XY: 3378 AN XY: 727092

African (AFR) AF: 0.000627 AC: 21 AN: 33468

American (AMR) AF: 0.000872 AC: 39 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00191 AC: 50 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00179 AC: 154 AN: 86244

European-Finnish (FIN) AF: 0.00301 AC: 161 AN: 53416

Middle Eastern (MID) AF: 0.000706 AC: 4 AN: 5662

European-Non Finnish (NFE) AF: 0.00569 AC: 6328 AN: 1111826

Other (OTH) AF: 0.00263 AC: 159 AN: 60378

GnomAD4 genome AF: 0.00289 AC: 440 AN: 152346 Hom.: 0 Cov.: 32 AF XY: 0.00275 AC XY: 205 AN XY: 74490

African (AFR) AF: 0.00103 AC: 43 AN: 41582

American (AMR) AF: 0.000654 AC: 10 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00339 AC: 36 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00492 AC: 335 AN: 68038

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00342 Hom.: 0

Bravo AF: 0.00269

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00491

EpiControl AF: 0.00445

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Familial temporal lobe epilepsy 5 (1)
-	-	1	Familial temporal lobe epilepsy 5;C3280734:Febrile seizures, familial, 11 (1)
-	-	1	Febrile seizures, familial, 11 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.62
DANN	Benign	0.48
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs138313759; hg19: chr8-68346339;