10-126038277-G-A

Variant summary

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

The NM_001288973.2(ADAM12):c.2313C>T(p.Gly771=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,612,220 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0080 (26 hom., cov: 32)
  • Exomes 𝑓: 0.00077 (23 hom.)
• Consequence: ADAM12 NM_001288973.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.158

Genes affected

ADAM12 (HGNC:190): (ADAM metallopeptidase domain 12) This gene encodes a member of a family of proteins that are structurally related to snake venom disintegrins and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. Expression of this gene has been used as a maternal serum marker for pre-natal development. Alternative splicing results in multiple transcript variants encoding different isoforms. Shorter isoforms are secreted, while longer isoforms are membrane-bound form. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-126038277-G-A is Benign according to our data. Variant chr10-126038277-G-A is described in ClinVar as [Benign]. Clinvar id is 783586.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.158 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.008 (1219/152316) while in subpopulation AFR AF= 0.0284 (1181/41560). AF 95% confidence interval is 0.0271. There are 26 homozygotes in gnomad4. There are 557 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM12	NM_001288973.2	c.2313C>T	p.Gly771=	synonymous_variant	20/23	ENST00000448723.2
ADAM12	NM_003474.6	c.2322C>T	p.Gly774=	synonymous_variant	20/23
ADAM12	XM_017016706.2	c.1155C>T	p.Gly385=	synonymous_variant	10/13
ADAM12	XM_024448210.1	c.984C>T	p.Gly328=	synonymous_variant	9/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM12	ENST00000448723.2	c.2313C>T	p.Gly771=	synonymous_variant	20/23	5	NM_001288973.2	A2
ADAM12	ENST00000368679.8	c.2322C>T	p.Gly774=	synonymous_variant	20/23	1		P2

Frequencies

GnomAD3 genomes AF: 0.00798 AC: 1214 AN: 152198 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00188 AC: 464 AN: 246168 Hom.: 9 AF XY: 0.00125 AC XY: 166 AN XY: 133032

Gnomad AFR exome AF: 0.0272

Gnomad AMR exome AF: 0.000732

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000101

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000269

Gnomad OTH exome AF: 0.000500

GnomAD4 exome AF: 0.000765 AC: 1117 AN: 1459904 Hom.: 23 Cov.: 31 AF XY: 0.000631 AC XY: 458 AN XY: 725988

Gnomad4 AFR exome AF: 0.0291

Gnomad4 AMR exome AF: 0.000853

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000702

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.00146

GnomAD4 genome AF: 0.00800 AC: 1219 AN: 152316 Hom.: 26 Cov.: 32 AF XY: 0.00748 AC XY: 557 AN XY: 74480

Gnomad4 AFR AF: 0.0284

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00374 Hom.: 3

Bravo AF: 0.00841

Asia WGS AF: 0.000577 AC: 2 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

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.1
Dann	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs114788194; hg19: chr10-127726846;