rs3745213

Variant names:

• chr19-40742104-C-T
• rs3745213
• ENST00000598352.1:c.472G>A
• ACTMAP p.Val158Ile

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000598352.1(ACTMAP):​c.472G>A​(p.Val158Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 542,780 control chromosomes in the GnomAD database, including 5,281 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/10 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1144 hom., cov: 32)
  • Exomes 𝑓: 0.14 (4137 hom.)
• Consequence: ACTMAP ENST00000598352.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 18 publications found

Genes affected

ACTMAP (HGNC:24758): (actin maturation protease)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.9102983E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000598352.1. 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
	ACTMAP	NM_198476.5	MANE Select	c.*329G>A		3_prime_UTR	Exon 6 of 6	NP_940878.3	Q5BKX5-1
	ACTMAP	NM_001353807.2		c.*329G>A		3_prime_UTR	Exon 7 of 7	NP_001340736.1
	ACTMAP	NM_001353806.2		c.*673G>A		3_prime_UTR	Exon 5 of 5	NP_001340735.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTMAP	ENST00000598352.1	TSL:1	c.472G>A	p.Val158Ile	missense	Exon 5 of 6	ENSP00000473024.1	M0R368
	ACTMAP	ENST00000378313.7	TSL:2 MANE Select	c.*329G>A		3_prime_UTR	Exon 6 of 6	ENSP00000367564.2	Q5BKX5-1
	ACTMAP	ENST00000862158.1		c.*329G>A		3_prime_UTR	Exon 6 of 6	ENSP00000532217.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16441 AN: 152024 Hom.: 1140 Cov.: 32

Gnomad AFR AF: 0.0360

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0789

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.114

GnomAD2 exomes AF: 0.138 AC: 18914 AN: 136968 AF XY: 0.140

Gnomad AFR exome AF: 0.0279

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.117

Gnomad EAS exome AF: 0.0692

Gnomad FIN exome AF: 0.148

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.137 AC: 53709 AN: 390638 Hom.: 4137 Cov.: 0 AF XY: 0.140 AC XY: 30312 AN XY: 216114

African (AFR) AF: 0.0324 AC: 384 AN: 11866

American (AMR) AF: 0.191 AC: 5668 AN: 29654

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 1715 AN: 14696

East Asian (EAS) AF: 0.110 AC: 1856 AN: 16854

South Asian (SAS) AF: 0.166 AC: 10043 AN: 60492

European-Finnish (FIN) AF: 0.150 AC: 2723 AN: 18210

Middle Eastern (MID) AF: 0.127 AC: 408 AN: 3214

European-Non Finnish (NFE) AF: 0.132 AC: 28383 AN: 215338

Other (OTH) AF: 0.124 AC: 2529 AN: 20314

GnomAD4 genome AF: 0.108 AC: 16456 AN: 152142 Hom.: 1144 Cov.: 32 AF XY: 0.110 AC XY: 8149 AN XY: 74366

African (AFR) AF: 0.0359 AC: 1491 AN: 41522

American (AMR) AF: 0.147 AC: 2250 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3468

East Asian (EAS) AF: 0.0789 AC: 409 AN: 5182

South Asian (SAS) AF: 0.163 AC: 788 AN: 4820

European-Finnish (FIN) AF: 0.150 AC: 1589 AN: 10574

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.135 AC: 9196 AN: 67974

Other (OTH) AF: 0.112 AC: 237 AN: 2114

Alfa AF: 0.123 Hom.: 2430

Bravo AF: 0.102

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.31
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.00089	T
PhyloP100		-1.2
Sift4G	Benign	0.47	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3745213;

hg19: chr19-41248009;

COSMIC: COSV54573339;

COSMIC: COSV54573339;