7-135034203-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_178563.4(AGBL3):c.612C>T(p.His204=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,551,520 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0061 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00063 (14 hom.)
• Consequence: AGBL3 NM_178563.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.578

Genes affected

AGBL3 (HGNC:27981): (AGBL carboxypeptidase 3) Enables metallocarboxypeptidase activity. Involved in protein side chain deglutamylation. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 7-135034203-C-T is Benign according to our data. Variant chr7-135034203-C-T is described in ClinVar as [Benign]. Clinvar id is 711016.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.578 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00614 (935/152242) while in subpopulation AFR AF= 0.0212 (881/41536). AF 95% confidence interval is 0.02. There are 8 homozygotes in gnomad4. There are 430 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL3	NM_178563.4	c.612C>T	p.His204=	synonymous_variant	7/17	ENST00000436302.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL3	ENST00000436302.6	c.612C>T	p.His204=	synonymous_variant	7/17	2	NM_178563.4	P2
AGBL3	ENST00000275763.10	c.612C>T	p.His204=	synonymous_variant, NMD_transcript_variant	7/17	1
AGBL3	ENST00000435976.6	c.612C>T	p.His204=	synonymous_variant	7/16	5		A2

Frequencies

GnomAD3 genomes AF: 0.00615 AC: 936 AN: 152124 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00256

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00146 AC: 227 AN: 156002 Hom.: 2 AF XY: 0.00100 AC XY: 83 AN XY: 82634

Gnomad AFR exome AF: 0.0250

Gnomad AMR exome AF: 0.000892

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000440

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000665

Gnomad OTH exome AF: 0.000457

GnomAD4 exome AF: 0.000635 AC: 888 AN: 1399278 Hom.: 14 Cov.: 29 AF XY: 0.000572 AC XY: 395 AN XY: 690144

Gnomad4 AFR exome AF: 0.0220

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.0000397

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000505

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000714

Gnomad4 OTH exome AF: 0.00116

GnomAD4 genome AF: 0.00614 AC: 935 AN: 152242 Hom.: 8 Cov.: 32 AF XY: 0.00578 AC XY: 430 AN XY: 74444

Gnomad4 AFR AF: 0.0212

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00269 Hom.: 5

Bravo AF: 0.00659

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	4.2
Dann	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs74319573; hg19: chr7-134718954;