5-90461202-C-A

Variant names:

• chr5-90461202-C-A
• NM_203406.2:c.805G>T

Variant summary

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

The NM_203406.2(MBLAC2):​c.805G>T​(p.Ala269Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MBLAC2 NM_203406.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.21

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

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=0.22505105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBLAC2	NM_203406.2	c.805G>T	p.Ala269Ser	missense_variant	Exon 2 of 2	ENST00000316610.7	NP_981951.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBLAC2	ENST00000316610.7	c.805G>T	p.Ala269Ser	missense_variant	Exon 2 of 2	1	NM_203406.2	ENSP00000314776.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459646 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726056

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.805G>T (p.A269S) alteration is located in exon 2 (coding exon 2) of the MBLAC2 gene. This alteration results from a G to T substitution at nucleotide position 805, causing the alanine (A) at amino acid position 269 to be replaced by a serine (S). 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	0.16
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.43	N
REVEL	Uncertain	0.31
Sift	Benign	0.036	D
Sift4G	Uncertain	0.046	D
Polyphen		0.81	P
Vest4		0.34
MutPred		0.36		Gain of disorder (P = 0.0151);
MVP		0.36
MPC		0.38
ClinPred		0.76	D
GERP RS		6.1
Varity_R		0.41
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-89757019;