NM_182924.4:c.2660A>C

Variant names:

• chr7-1434651-T-G
• rs138745697
• NM_182924.4:c.2660A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_182924.4(MICALL2):​c.2660A>C​(p.Lys887Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 1,567,926 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (10 hom., cov: 34)
  • Exomes 𝑓: 0.0044 (50 hom.)
• Consequence: MICALL2 NM_182924.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.513
• Publications: 9 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0042794943).
• BP6: Variant 7-1434651-T-G is Benign according to our data. Variant chr7-1434651-T-G is described in ClinVar as Benign. ClinVar VariationId is 781891.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00437 (6192/1415564) while in subpopulation MID AF = 0.0215 (119/5542). AF 95% confidence interval is 0.0183. There are 50 homozygotes in GnomAdExome4. There are 3402 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

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.2660A>C	p.Lys887Thr	missense	Exon 17 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.2660A>C	p.Lys887Thr	missense	Exon 17 of 17	ENSP00000297508.7	Q8IY33-1
	MICALL2	ENST00000873416.1		c.2645A>C	p.Lys882Thr	missense	Exon 17 of 17	ENSP00000543475.1
	MICALL2	ENST00000873414.1		c.2636A>C	p.Lys879Thr	missense	Exon 17 of 17	ENSP00000543473.1

Frequencies

GnomAD3 genomes AF: 0.00378 AC: 575 AN: 152244 Hom.: 10 Cov.: 34

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.0527

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0167

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00342

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00670 AC: 1431 AN: 213670 AF XY: 0.00740

Gnomad AFR exome AF: 0.000256

Gnomad AMR exome AF: 0.00429

Gnomad ASJ exome AF: 0.0591

Gnomad EAS exome AF: 0.0000619

Gnomad FIN exome AF: 0.000152

Gnomad NFE exome AF: 0.00410

Gnomad OTH exome AF: 0.0105

GnomAD4 exome AF: 0.00437 AC: 6192 AN: 1415564 Hom.: 50 Cov.: 31 AF XY: 0.00485 AC XY: 3402 AN XY: 701244

African (AFR) AF: 0.000936 AC: 29 AN: 30988

American (AMR) AF: 0.00443 AC: 146 AN: 32984

Ashkenazi Jewish (ASJ) AF: 0.0545 AC: 1288 AN: 23626

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39220

South Asian (SAS) AF: 0.0163 AC: 1307 AN: 80112

European-Finnish (FIN) AF: 0.000231 AC: 12 AN: 51964

Middle Eastern (MID) AF: 0.0215 AC: 119 AN: 5542

European-Non Finnish (NFE) AF: 0.00263 AC: 2875 AN: 1093122

Other (OTH) AF: 0.00715 AC: 415 AN: 58006

GnomAD4 genome AF: 0.00377 AC: 575 AN: 152362 Hom.: 10 Cov.: 34 AF XY: 0.00387 AC XY: 288 AN XY: 74504

African (AFR) AF: 0.000529 AC: 22 AN: 41588

American (AMR) AF: 0.00261 AC: 40 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0527 AC: 183 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0168 AC: 81 AN: 4834

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00343 AC: 233 AN: 68028

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00604 Hom.: 12

Bravo AF: 0.00365

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00285 AC: 11

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00558 AC: 48

ExAC AF: 0.00734 AC: 891

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.51
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.072
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.032	D
Polyphen		0.97	D
Vest4		0.33
MVP		0.81
MPC		0.056
ClinPred		0.043	T
GERP RS		0.53
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.4
Varity_R		0.13
gMVP		0.50
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: rs138745697; hg19: chr7-1474287; COSMIC: COSV52517023; COSMIC: COSV52517023;