rs3745213

Positions:

• chr19-40742104-C-T

Variant summary

Our verdict is Benign. Variant got -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. 8/9 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

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTMAP	NM_198476.5	c.*329G>A		3_prime_UTR_variant	6/6	ENST00000378313.7	NP_940878.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTMAP	ENST00000378313	c.*329G>A		3_prime_UTR_variant	6/6	2	NM_198476.5	ENSP00000367564.2

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

GnomAD3 exomes AF: 0.138 AC: 18914 AN: 136968 Hom.: 1492 AF XY: 0.140 AC XY: 10376 AN XY: 74338

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 SAS exome AF: 0.166

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

Gnomad4 AFR exome AF: 0.0324

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.110

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.124

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

Gnomad4 AFR AF: 0.0359

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0789

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.112

Alfa AF: 0.129 Hom.: 1576

Bravo AF: 0.102

TwinsUK AF: 0.129 AC: 478

ALSPAC AF: 0.132 AC: 509

ExAC AF: 0.105 AC: 2109

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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
Sift4G	Benign	0.47	T
GERP RS		-6.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3745213; hg19: chr19-41248009; COSMIC: COSV54573339; COSMIC: COSV54573339;