chr5-90474001-C-A

Variant names:

• chr5-90474001-C-A
• rs1179934133
• NM_203406.2:c.292G>T

Variant summary

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

The NM_203406.2(MBLAC2):​c.292G>T​(p.Val98Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,374 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V98M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MBLAC2 NM_203406.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.22

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBLAC2	NM_203406.2	c.292G>T	p.Val98Leu	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.292G>T	p.Val98Leu	missense_variant	Exon 1 of 2	1	NM_203406.2	ENSP00000314776.6
MBLAC2	ENST00000514906.1	c.292G>T	p.Val98Leu	missense_variant	Exon 1 of 1	6		ENSP00000425600.1
POLR3G	ENST00000512239.1	c.-44+2075C>A		intron_variant	Intron 1 of 1	5		ENSP00000424970.1
POLR3G	ENST00000505345.5	c.-361C>A		upstream_gene_variant		3		ENSP00000427412.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1446374 Hom.: 0 Cov.: 36 AF XY: 0.00000139 AC XY: 1 AN XY: 718162

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000511

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T;T
M_CAP	Pathogenic	0.40	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	0.19	N;N
REVEL	Uncertain	0.43
Sift	Benign	0.50	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.89	P;.
Vest4		0.64
MutPred		0.51		Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);
MVP		0.43
MPC		0.75
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.43
gMVP		0.77

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: rs1179934133; hg19: chr5-89769818;