5-90473925-C-T

Variant names:

• chr5-90473925-C-T
• NM_203406.2:c.368G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203406.2(MBLAC2):​c.368G>A​(p.Ser123Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MBLAC2 NM_203406.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.31

Genes affected

MBLAC2 (HGNC:33711): (metallo-beta-lactamase domain containing 2) Enables palmitoyl-CoA hydrolase activity. Located in endoplasmic reticulum membrane and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

POLR3G (HGNC:30075): (RNA polymerase III subunit G) Enables chromatin binding activity. Involved in positive regulation of innate immune response; positive regulation of interferon-beta production; and transcription by RNA polymerase III. Acts upstream of or within cell population proliferation. Located in cytosol and nuclear body. Part of RNA polymerase III complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1402537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBLAC2	NM_203406.2	c.368G>A	p.Ser123Asn	missense_variant	Exon 1 of 2	ENST00000316610.7	NP_981951.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBLAC2	ENST00000316610.7	c.368G>A	p.Ser123Asn	missense_variant	Exon 1 of 2	1	NM_203406.2	ENSP00000314776.6
MBLAC2	ENST00000514906.1	c.368G>A	p.Ser123Asn	missense_variant	Exon 1 of 1	6		ENSP00000425600.1
POLR3G	ENST00000512239.1	c.-44+1999C>T		intron_variant	Intron 1 of 1	5		ENSP00000424970.1
POLR3G	ENST00000505345.5	c.-437C>T		upstream_gene_variant		3		ENSP00000427412.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1453268 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 722152

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.368G>A (p.S123N) alteration is located in exon 1 (coding exon 1) of the MBLAC2 gene. This alteration results from a G to A substitution at nucleotide position 368, causing the serine (S) at amino acid position 123 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;.
Eigen	Benign	0.029
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.30	N;N
REVEL	Benign	0.061
Sift	Benign	0.48	T;T
Sift4G	Benign	0.53	T;T
Polyphen		0.0070	B;.
Vest4		0.18
MutPred		0.45		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP		0.095
MPC		0.40
ClinPred		0.78	D
GERP RS		5.2
Varity_R		0.40
gMVP		0.66

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-89769742;