12-57232167-G-A

Position:

• chr12-57232167-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005412.6(SHMT2):​c.513-44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,560,148 control chromosomes in the GnomAD database, including 423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (94 hom., cov: 33)
  • Exomes 𝑓: 0.011 (329 hom.)
• Consequence: SHMT2 NM_005412.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.250

Genes affected

SHMT2 (HGNC:10852): (serine hydroxymethyltransferase 2) This gene encodes the mitochondrial form of a pyridoxal phosphate-dependent enzyme that catalyzes the reversible reaction of serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. The encoded product is primarily responsible for glycine synthesis. The activity of the encoded protein has been suggested to be the primary source of intracellular glycine. The gene which encodes the cytosolic form of this enzyme is located on chromosome 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

SHMT2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-57232167-G-A is Benign according to our data. Variant chr12-57232167-G-A is described in ClinVar as [Benign]. Clinvar id is 1234301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHMT2	NM_005412.6	c.513-44G>A		intron_variant		ENST00000328923.8	NP_005403.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHMT2	ENST00000328923.8	c.513-44G>A		intron_variant		1	NM_005412.6	ENSP00000333667.3

Frequencies

GnomAD3 genomes AF: 0.0240 AC: 3646 AN: 152128 Hom.: 95 Cov.: 33

Gnomad AFR AF: 0.0581

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00819

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.0881

Gnomad SAS AF: 0.0216

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00719

Gnomad OTH AF: 0.0201

GnomAD3 exomes AF: 0.0156 AC: 3899 AN: 249680 Hom.: 105 AF XY: 0.0147 AC XY: 1987 AN XY: 135074

Gnomad AFR exome AF: 0.0587

Gnomad AMR exome AF: 0.00411

Gnomad ASJ exome AF: 0.00450

Gnomad EAS exome AF: 0.0789

Gnomad SAS exome AF: 0.0173

Gnomad FIN exome AF: 0.00190

Gnomad NFE exome AF: 0.00607

Gnomad OTH exome AF: 0.0108

GnomAD4 exome AF: 0.0115 AC: 16172 AN: 1407902 Hom.: 329 Cov.: 26 AF XY: 0.0114 AC XY: 8028 AN XY: 703972

Gnomad4 AFR exome AF: 0.0615

Gnomad4 AMR exome AF: 0.00493

Gnomad4 ASJ exome AF: 0.00543

Gnomad4 EAS exome AF: 0.0929

Gnomad4 SAS exome AF: 0.0179

Gnomad4 FIN exome AF: 0.00152

Gnomad4 NFE exome AF: 0.00723

Gnomad4 OTH exome AF: 0.0135

GnomAD4 genome AF: 0.0240 AC: 3656 AN: 152246 Hom.: 94 Cov.: 33 AF XY: 0.0245 AC XY: 1826 AN XY: 74438

Gnomad4 AFR AF: 0.0582

Gnomad4 AMR AF: 0.00818

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.0883

Gnomad4 SAS AF: 0.0216

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00719

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0184 Hom.: 9

Bravo AF: 0.0259

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.24
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs74093117; hg19: chr12-57625950;