5-90461238-C-T

Variant names:

• chr5-90461238-C-T
• rs750601777
• NM_203406.2:c.769G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203406.2(MBLAC2):​c.769G>A​(p.Val257Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. V257L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MBLAC2 NM_203406.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.628
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.098447144).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203406.2. 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
	MBLAC2	NM_203406.2	MANE Select	c.769G>A	p.Val257Ile	missense	Exon 2 of 2	NP_981951.2	Q68D91-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBLAC2	ENST00000316610.7	TSL:1 MANE Select	c.769G>A	p.Val257Ile	missense	Exon 2 of 2	ENSP00000314776.6	Q68D91-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.028
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.63
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.10
Sift	Benign	0.24	T
Sift4G	Benign	0.53	T
Polyphen		0.0020	B
Vest4		0.12
MutPred		0.40		Loss of helix (P = 0.079)
MVP		0.20
MPC		0.29
ClinPred		0.38	T
GERP RS		5.2
Varity_R		0.044
gMVP		0.53
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs750601777; hg19: chr5-89757055;