7-1437543-G-C

Variant names:

• chr7-1437543-G-C
• rs1230479669
• NM_182924.4:c.2468C>G

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.2468C>G​(p.Ala823Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,375,374 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. A823V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: MICALL2 NM_182924.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• 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=0.1372053).

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.2468C>G	p.Ala823Gly	missense	Exon 14 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.2468C>G	p.Ala823Gly	missense	Exon 14 of 17	ENSP00000297508.7	Q8IY33-1
	MICALL2	ENST00000873416.1		c.2453C>G	p.Ala818Gly	missense	Exon 14 of 17	ENSP00000543475.1
	MICALL2	ENST00000873414.1		c.2444C>G	p.Ala815Gly	missense	Exon 14 of 17	ENSP00000543473.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1375374 Hom.: 0 Cov.: 32 AF XY: 0.00000147 AC XY: 1 AN XY: 678970

African (AFR) AF: 0.00 AC: 0 AN: 30174

American (AMR) AF: 0.00 AC: 0 AN: 33056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24756

East Asian (EAS) AF: 0.00 AC: 0 AN: 35420

South Asian (SAS) AF: 0.00 AC: 0 AN: 78390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4414

European-Non Finnish (NFE) AF: 9.30e-7 AC: 1 AN: 1075818

Other (OTH) AF: 0.00 AC: 0 AN: 57306

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.89
DEOGEN2	Benign	0.0084	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.077
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.026
Sift	Benign	0.44	T
Sift4G	Benign	0.26	T
Polyphen		0.65	P
Vest4		0.15
MutPred		0.23		Gain of loop (P = 0.0013)
MVP		0.35
MPC		0.016
ClinPred		0.14	T
GERP RS		0.99
Varity_R		0.044
gMVP		0.069
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1230479669; hg19: chr7-1477179;