7-1436800-C-A

Variant names:

• chr7-1436800-C-A
• rs370800124
• NM_182924.4:c.2533G>T

Variant summary

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

The NM_182924.4(MICALL2):​c.2533G>T​(p.Val845Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,100 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V845M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MICALL2 NM_182924.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 0 publications found

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

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=0.15031049).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182924.4. 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
	MICALL2	NM_182924.4	MANE Select	c.2533G>T	p.Val845Leu	missense	Exon 15 of 17	NP_891554.1	Q8IY33-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICALL2	ENST00000297508.8	TSL:1 MANE Select	c.2533G>T	p.Val845Leu	missense	Exon 15 of 17	ENSP00000297508.7	Q8IY33-1
	MICALL2	ENST00000873416.1		c.2518G>T	p.Val840Leu	missense	Exon 15 of 17	ENSP00000543475.1
	MICALL2	ENST00000873414.1		c.2509G>T	p.Val837Leu	missense	Exon 15 of 17	ENSP00000543473.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456100 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724426

African (AFR) AF: 0.00 AC: 0 AN: 33148

American (AMR) AF: 0.00 AC: 0 AN: 44426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26046

East Asian (EAS) AF: 0.00 AC: 0 AN: 39244

South Asian (SAS) AF: 0.00 AC: 0 AN: 85920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110510

Other (OTH) AF: 0.00 AC: 0 AN: 60186

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.88
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.93	L
PhyloP100		1.2
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.047
Sift	Benign	0.26	T
Sift4G	Benign	0.47	T
Polyphen		0.90	P
Vest4		0.33
MutPred		0.29		Gain of loop (P = 0.1081)
MVP		0.38
MPC		0.027
ClinPred		0.35	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.043
gMVP		0.26
Mutation Taster		=93/7	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: rs370800124; hg19: chr7-1476436; COSMIC: COSV52516729; COSMIC: COSV52516729;