7-1437897-T-C

Position:

• chr7-1437897-T-C

Variant summary

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

The NM_182924.4(MICALL2):​c.2395A>G​(p.Met799Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000358 in 1,396,668 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: 0.0000036 (0 hom.)
• Consequence: MICALL2 NM_182924.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.87

Genes affected

MICALL2 (HGNC:29672): (MICAL like 2) Enables filamin binding activity. Involved in positive regulation of protein targeting to mitochondrion. Predicted to be located in several cellular components, including bicellular tight junction; neuron projection; and recycling endosome. Predicted to colocalize with stress fiber. [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=0.1501897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICALL2	NM_182924.4	c.2395A>G	p.Met799Val	missense_variant	13/17	ENST00000297508.8	NP_891554.1
MICALL2	XM_047420838.1	c.1162A>G	p.Met388Val	missense_variant	7/11		XP_047276794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICALL2	ENST00000297508.8	c.2395A>G	p.Met799Val	missense_variant	13/17	1	NM_182924.4	ENSP00000297508	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000358 AC: 5 AN: 1396668 Hom.: 0 Cov.: 32 AF XY: 0.00000290 AC XY: 2 AN XY: 688892

Gnomad4 AFR exome AF: 0.0000634

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: 0.00000278

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ESP6500AA AF: 0.000246 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000128 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2022

The c.2395A>G (p.M799V) alteration is located in exon 13 (coding exon 13) of the MICALL2 gene. This alteration results from a A to G substitution at nucleotide position 2395, causing the methionine (M) at amino acid position 799 to be replaced by a valine (V). 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	0.18
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0074	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	0.91	D;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.082
Sift	Benign	0.32	T
Sift4G	Benign	1.0	T
Polyphen		0.13	B
Vest4		0.30
MVP		0.39
MPC		0.076
ClinPred		0.71	D
GERP RS		3.5
Varity_R		0.12
gMVP		0.29

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: rs138288683; hg19: chr7-1477533;