rs147086028

Variant names:

• chr12-56300197-G-C
• rs147086028
• NM_004077.3:c.5C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-56300197-G-C
• chr12-56300197-G-A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004077.3(CS):​c.5C>G​(p.Ala2Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000115 in 1,568,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: CS NM_004077.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.44
• Publications: 4 publications found

Genes affected

CS (HGNC:2422): (citrate synthase) The protein encoded by this gene is a Krebs tricarboxylic acid cycle enzyme that catalyzes the synthesis of citrate from oxaloacetate and acetyl coenzyme A. The enzyme is found in nearly all cells capable of oxidative metablism. This protein is nuclear encoded and transported into the mitochondrial matrix, where the mature form is found. [provided by RefSeq, Jul 2008]

ENSG00000144785 (HGNC:):

CNPY2-AS1 (HGNC:55480): (CNPY2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.051139772).
• BS2: High AC in GnomAd4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004077.3. 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
	CS	NM_004077.3	MANE Select	c.5C>G	p.Ala2Gly	missense	Exon 1 of 11	NP_004068.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CS	ENST00000351328.8	TSL:1 MANE Select	c.5C>G	p.Ala2Gly	missense	Exon 1 of 11	ENSP00000342056.3	O75390
	ENSG00000144785	ENST00000549318.5	TSL:5	c.593C>G	p.Ala198Gly	missense	Exon 7 of 9	ENSP00000446743.1	F8W031
	CS	ENST00000548567.5	TSL:1	c.-277C>G		5_prime_UTR	Exon 1 of 12	ENSP00000446779.1	A0A0C4DGI3

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152250 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000246 AC: 44 AN: 178940 AF XY: 0.000238

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.00103

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000121

Gnomad NFE exome AF: 0.000160

Gnomad OTH exome AF: 0.000842

GnomAD4 exome AF: 0.000119 AC: 168 AN: 1416176 Hom.: 0 Cov.: 30 AF XY: 0.000130 AC XY: 91 AN XY: 701152

African (AFR) AF: 0.0000314 AC: 1 AN: 31812

American (AMR) AF: 0.000531 AC: 20 AN: 37672

Ashkenazi Jewish (ASJ) AF: 0.00142 AC: 36 AN: 25292

East Asian (EAS) AF: 0.00 AC: 0 AN: 36786

South Asian (SAS) AF: 0.0000370 AC: 3 AN: 81050

European-Finnish (FIN) AF: 0.0000596 AC: 3 AN: 50304

Middle Eastern (MID) AF: 0.00221 AC: 9 AN: 4066

European-Non Finnish (NFE) AF: 0.0000743 AC: 81 AN: 1090704

Other (OTH) AF: 0.000256 AC: 15 AN: 58490

GnomAD4 genome AF: 0.0000853 AC: 13 AN: 152368 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74514

African (AFR) AF: 0.0000481 AC: 2 AN: 41592

American (AMR) AF: 0.0000653 AC: 1 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68026

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000228 Hom.: 1

Bravo AF: 0.0000945

ExAC AF: 0.000152 AC: 18

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.024
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.4
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.29
Sift	Uncertain	0.014	D
Sift4G	Benign	0.13	T
Polyphen		0.012	B
Vest4		0.34
MVP		0.40
MPC		0.069
ClinPred		0.10	T
GERP RS		4.7
PromoterAI		-0.18	Neutral
Varity_R		0.43
gMVP		0.55
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs147086028; hg19: chr12-56693981;